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Mouse strain-dependent neutralizing antibody responses to Zika virus vaccines: Sang Hwan Seo, Jung-ah Choi, Eunji Yang, Hayan Park, Dae-Im Jung, Jae-Ouk Kim, Jae Seung Yang, Manki Song; J. Microbiol. 2025;63(8):e2504005. Published online August 31, 2025; DOI: https://doi.org/10.71150/jm.2504005

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The 2015 Zika virus (ZIKV) outbreak in Brazil and its global spread underscored the urgent need for effective and broadly protective vaccines. While C57BL/6 and BALB/c mice are widely used in preclinical vaccine research, direct comparisons of their ability to elicit ZIKV-specific neutralizing antibodies (nAbs) remain limited. This study aimed to systematically evaluate and compare the immunogenic potential of these two common mouse strains across diverse vaccine platforms, focusing on their capacity to generate functional neutralizing antibody responses. We assessed nAb and IgG responses following four vaccination strategies: (1) DNA vaccine encoding prMEΔTM followed by E protein domain III boost, (2) recombinant EΔTM protein expressed using baculovirus system, (3) formalin-inactivated ZIKV, and (4) live ZIKV. Although both strains generated detectable ZIKV- and E protein-specific IgG, the magnitude and quality of responses varied by vaccine platform and strain. Notably, C57BL/6 mice consistently mounted significantly higher nAb titers than BALB/c mice across all immunization groups, including subunit- and whole-virus-based vaccines. In contrast, BALB/c mice showed lower or undetectable nAb responses, despite comparable or higher total IgG levels in some cases. These findings show that host genetic background is a critical determinant of vaccine-induced neutralization and underscore the importance of selecting appropriate animal models in ZIKV vaccine development. C57BL/6 mice, due to their robust nAb responses, represent a reliable model for evaluating vaccine immunogenicity. Conversely, the limited nAb responses in BALB/c mice position them as a potential low-responder model, offering a stringent system to test the potency and breadth of protective immunity under suboptimal conditions.

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The Pathogenesis and Virulence of the Major Enterovirus Pathogens Associated with Severe Clinical Manifestations: A Comprehensive Review
Yuwei Liu, Maiheliya Maisimu, Zhihang Ge, Suling Xiao, Haoran Wang
Cells.2025; 14(20): 1617. CrossRef

Reviews

Advancements in dengue vaccines: A historical overview and pro-spects for following next-generation candidates: Kai Yan, Lingjing Mao, Jiaming Lan, Zhongdang Xiao; J. Microbiol. 2025;63(2):e2410018. Published online February 27, 2025; DOI: https://doi.org/10.71150/jm.2410018

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Dengue, caused by four serotypes of dengue viruses (DENV-1 to DENV-4), is the most prevalent and widely mosquito-borne viral disease affecting humans. Dengue virus (DENV) infection has been reported in over 100 countries, and approximately half of the world's population is now at risk. The paucity of universally licensed DENV vaccines highlights the urgent need to address this public health concern. Action and attention to antibody-dependent enhancement increase the difficulty of vaccine development. With the worsening dengue fever epidemic, Dengvaxia^® (CYD-TDV) and Qdenga^® (TAK-003) have been approved for use in specific populations in affected areas. However, these vaccines do not provide a balanced immune response to all four DENV serotypes and the vaccination cannot cover all populations. There is still a need to develop a safe, broad-spectrum, and effective vaccine to address the increasing number of dengue cases worldwide. This review provides an overview of the existing DENV vaccines, as well as potential candidates for future studies on DENV vaccine development, and discusses the challenges and possible solutions in the field.

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Role of c-ABL in DENV-2 Infection and Actin Remodeling in Vero Cells
Grace Paola Carreño-Flórez, Alexandra Milena Cuartas-López, Ryan L. Boudreau, Miguel Vicente-Manzanares, Juan Carlos Gallego-Gómez
International Journal of Molecular Sciences.2025; 26(9): 4206. CrossRef
Crystallographic Fragment Screening of the Dengue Virus Polymerase Reveals Multiple Binding Sites for the Development of Non-nucleoside Antiflavivirals
Manisha Saini, Jasmin C. Aschenbrenner, Francesc Xavier Ruiz, Ashima Chopra, Anu V. Chandran, Peter G. Marples, Blake H. Balcomb, Daren Fearon, Frank von Delft, Eddy Arnold
Journal of Medicinal Chemistry.2025; 68(17): 18356. CrossRef
Understanding the Diversity of Dengue Serotypes: Impacts on Public Health and Disease Control
Gopinath Ramalingam, Madhumitha Patchaiyappan, M. Arundadhi, Krishnapriya Subramani, A. Dhanasezhian, Sucila Thangam Ganesan
The Journal of Medical Research.2025; 11(4): 69. CrossRef
Dengue Fever Resurgence in Iran: An Integrative Review of Causative Factors and Control Strategies
Seyed Hassan Nikookar, Saeedeh Hoseini, Omid Dehghan, Mahmoud Fazelidinan, Ahmadali Enayati
Tropical Medicine and Infectious Disease.2025; 10(11): 309. CrossRef
Enhancement of viral infection by antibodies and consequences
Corentin Morvan, Magloire Pandoua Nekoua, Cyril Debuysschere, Enagnon Kazali Alidjinou, Didier Hober, Sebla Bulent Kutluay
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Microbial Volatiles from Human Skin and Floral Nectar: Insufficiently Understood Adult Feeding Cues To Improve Odor-Based Traps for Aedes Vector Control
Simon Malassigné, Claire Valiente Moro, Patricia Luis
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An interpretable machine learning model for dengue detection with clinical hematological data
Izaz Ahmmed Tuhin, A.K.M.Fazlul Kobir Siam, Md Mahfuzur Rahman Shanto, Md Rajib Mia, Imran Mahmud, Apurba Ghosh
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Recent Advances of Nipah Virus Disease: Pathobiology to Treatment and Vaccine Advancement: Sagnik Saha, Manojit Bhattacharya, Sang-Soo Lee, Chiranjib Chakraborty; J. Microbiol. 2024;62(10):811-828. Published online September 18, 2024; DOI: https://doi.org/10.1007/s12275-024-00168-3

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The zoonotic infection of the Nipah virus (NiV) has yet again appeared in 2023 in Kerala state, India. The virus, which has a mortality rate ranging from about 40 to 70%, has already infected India five times, the first being in 2001. The current infection is the sixth virus outbreak in the Indian population. In 1998, the first NiV infection was noted in one village in Malaysia. After that, outbreaks from other South and Southeast Asian countries have been reported periodically. It can spread between humans through contact with body fluids. Therefore, it is unlikely to generate a new pandemic. However, there is a considerable knowledge gap in the different areas of NiV. To date, no approved vaccines or treatments have been available. To fulfil the knowledge gap, the review article provided a detailed overview of the genome and genome-encoded proteins, epidemiology, transmission, pathobiology, immunobiology, diagnosis, prevention and control measures, therapeutics (monoclonal antibodies and drug molecules), and vaccine advancement of the emerging and deadly pathogen. The advanced information will help researchers to develop safe and effective NiV vaccine and treatment regimens worldwide.

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An Overview of Nipah Virus Infection
Ujjawal Singh, Ramsha Sharma, Raj Kamal, Ranjeet Kumar
Anti-Infective Agents.2025;[Epub] CrossRef
Antiviral effects of heme oxygenase-1 against canine coronavirus and canine influenza virus in vitro
Jae-Hyeong Kim, Dong-Hwi Kim, Kyu-Beom Lim, Joong-Bok Lee, Seung-Yong Park, Chang-Seon Song, Sang-Won Lee, Dong-Hun Lee, Do-Geun Kim, Hun-Young Yoon, In-Soo Choi
Journal of Microbiology.2025; 63(5): e2501029. CrossRef
Efficient and modular reverse genetics system for rapid generation of recombinant severe acute respiratory syndrome coronavirus 2
Sojung Bae, Jinjong Myoung
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Adenoviral Vector System: A Comprehensive Overview of Constructions, Therapeutic Applications and Host Responses: Anyeseu Park, Jeong Yoon Lee; J. Microbiol. 2024;62(7):491-509. Published online July 22, 2024; DOI: https://doi.org/10.1007/s12275-024-00159-4

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Adenoviral vectors are crucial for gene therapy and vaccine development, offering a platform for gene delivery into host cells. Since the discovery of adenoviruses, first-generation vectors with limited capacity have evolved to third-generation vectors flacking viral coding sequences, balancing safety and gene-carrying capacity. The applications of adenoviral vectors for gene therapy and anti-viral treatments have expanded through the use of in vitro ligation and homologous recombination, along with gene editing advancements such as CRISPR-Cas9. Current research aims to maintain the efficacy and safety of adenoviral vectors by addressing challenges such as pre-existing immunity against adenoviral vectors and developing new adenoviral vectors from rare adenovirus types and non-human species. In summary, adenoviral vectors have great potential in gene therapy and vaccine development. Through continuous research and technological advancements, these vectors are expected to lead to the development of safer and more effective treatments.

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Engineering an oncolytic adenoviral platform for precise delivery of antisense peptide nucleic acid to modulate PD-L1 overexpression in cancer cells
Andrea Patrizia Falanga, Francesca Greco, Monica Terracciano, Stefano D’Errico, Maria Marzano, Sara Feola, Valentina Sepe, Flavia Fontana, Ilaria Piccialli, Vincenzo Cerullo, Hélder A. Santos, Nicola Borbone
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Enhancing precision in cancer treatment: the role of gene therapy and immune modulation in oncology
Emile Youssef, Brandon Fletcher, Dannelle Palmer
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Protein-Based Degraders: From Chemical Biology Tools to Neo-Therapeutics
Lisha Ou, Mekedlawit T. Setegne, Jeandele Elliot, Fangfang Shen, Laura M. K. Dassama
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Intestinal mucus: the unsung hero in the battle against viral gastroenteritis
Waqar Saleem, Ateeqa Aslam, Mehlayl Tariq, Hans Nauwynck
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Chromatin structure and gene transcription of recombinant p53 adenovirus vector within host
Duo Ning, Yuqing Deng, Simon Zhongyuan Tian
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Ke-Ke Feng, Cheng-Lei Li, Yi-Fan Tu, Shi-Cheng Tian, Rui Xiong, Bai-Sheng Sa, Jing-Wei Shao
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Yilin Bao, Yue Hu, Mengxuan Hao, Qinmeng Zhang, Guoli Yang, Zhiwei Jiang
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Tian Yu, Xiaohong Chen
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Qian Hu, Jie Huang, Xiangmin Zhang, Haoru Wang, Xiaoying Ni, Huiru Zhu, Jinhua Cai
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Bo He, Belinda Wilson, Shih-Heng Chen, Kedar Sharma, Erica Scappini, Molly Cook, Robert Petrovich, Negin P. Martin
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Journal Articles

Vaccine Development for Severe Fever with Thrombocytopenia Syndrome Virus in Dogs: Seok-Chan Park, Da-Eun Jeong, Sun-Woo Han, Joon-Seok Chae, Joo-Yong Lee, Hyun-Sook Kim, Bumseok Kim, Jun-Gu Kang; J. Microbiol. 2024;62(4):327-335. Published online April 18, 2024; DOI: https://doi.org/10.1007/s12275-024-00119-y

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Abstract PDF

Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening viral zoonosis. The causative agent of this disease is the Dabie bandavirus, which is usually known as the SFTS virus (SFTSV). Although the role of vertebrates in SFTSV transmission to humans remains uncertain, some reports have suggested that dogs could potentially transmit SFTSV to humans. Consequently, preventive measures against SFTSV in dogs are urgently needed. In the present study, dogs were immunized three times at two-week intervals with formaldehyde-inactivated SFTSV with two types of adjuvants. SFTSV (KCD46) was injected into all dogs two weeks after the final immunization. Control dogs showed viremia from 2 to 4 days post infection (dpi), and displayed white pulp atrophy in the spleen, along with a high level of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay (TUNEL) positive area. However, the inactivated SFTSV vaccine groups exhibited rare pathological changes and significantly reduced TUNEL positive areas in the spleen. Furthermore, SFTSV viral loads were not detected at any of the tested dpi. Our results indicate that both adjuvants can be safely used in combination with an inactivated SFTSV formulation to induce strong neutralizing antibodies. Inactivated SFTSV vaccines effectively prevent pathogenicity and viremia in dogs infected with SFTSV. In conclusion, our study highlighted the potential of inactivated SFTSV vaccination for SFTSV control in dogs.

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The immunogenicity and protection efficacy evaluation of mRNA vaccine candidate for severe fever with thrombocytopenia syndrome in mice
Da-Eun Jeong, Jack Yoon, Baek Kim, Jun-Gu Kang, Abdallah M. Samy
PLOS Neglected Tropical Diseases.2025; 19(4): e0012999. CrossRef
Efficient and modular reverse genetics system for rapid generation of recombinant severe acute respiratory syndrome coronavirus 2
Sojung Bae, Jinjong Myoung
Journal of Microbiology.2025; 63(7): e2504015. CrossRef
Current status of severe fever with thrombocytopenia syndrome in China (Review)
Hao Sun, Quanman Hu, Saiwei Lu, Yanyan Yang, Li Zhang, Jinzhao Long, Yuefei Jin, Haiyan Yang, Shuaiyin Chen, Guangcai Duan
International Journal of Molecular Medicine.2025; 56(5): 1. CrossRef
Domain-Specific Impacts of Spike Protein Mutations on Infectivity and Antibody Escape in SARS-CoV-2 Omicron BA.1
Tae-Hun Kim, Sojung Bae, Jinjong Myoung
Journal of Microbiology and Biotechnology.2025;[Epub] CrossRef

Lactobacillus acidophilus KBL409 Ameliorates Atopic Dermatitis in a Mouse Model: Woon-ki Kim , You Jin Jang , SungJun Park , Sung-gyu Min , Heeun Kwon , Min Jung Jo , GwangPyo Ko; J. Microbiol. 2024;62(2):91-99. Published online February 22, 2024; DOI: https://doi.org/10.1007/s12275-024-00104-5

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Atopic dermatitis (AD) is a chronic inflammatory skin disease with repeated exacerbations of eczema and pruritus. Probiotics can prevent or treat AD appropriately via modulation of immune responses and gut microbiota. In this study, we evaluated effects of Lactobacillus acidophilus (L. acidophilus) KBL409 using a house dust mite (Dermatophagoides farinae)-induced in vivo AD model. Oral administration of L. acidophilus KBL409 significantly reduced dermatitis scores and decreased infiltration of immune cells in skin tissues. L. acidophilus KBL409 reduced in serum immunoglobulin E and mRNA levels of T helper (Th)1 (Interferon-γ), Th2 (Interleukin [IL]-4, IL-5, IL-13, and IL-31), and Th17 (IL-17A) cytokines in skin tissues. The anti-inflammatory cytokine IL-10 was increased and Foxp3 expression was up-regulated in AD-induced mice with L. acidophilus KBL409. Furthermore, L. acidophilus KBL409 significantly modulated gut microbiota and concentrations of short-chain fatty acids and amino acids, which could explain its effects on AD. Our results suggest that L. acidophilus KBL409 is the potential probiotic for AD treatment by modulating of immune responses and gut microbiota of host.

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Limosilactobacillus fermentum KBL674 Alleviates Vaginal Candidiasis
Sung Jae Jang, Eun Jung Jo, Cheonghoon Lee, Bo-Ram Cho, Yun Jeong Shin, Jun Soo Song, Woon-Ki Kim, Nanhee Lee, Hyungjin Lee, SungJun Park, GwangPyo Ko
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The gut-skin axis: a bi-directional, microbiota-driven relationship with therapeutic potential
Maira Jimenez-Sanchez, Larissa S. Celiberto, Hyungjun Yang, Ho Pan Sham, Bruce A. Vallance
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Probiotics ameliorate atopic dermatitis by modulating the dysbiosis of the gut microbiota in dogs
Hyokeun Song, Seung-Hyun Mun, Dae-Woong Han, Jung-Hun Kang, Jae-Uk An, Cheol-Yong Hwang, Seongbeom Cho
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The effect of daily oral probiotic and postbiotic supplementation on the canine skin microbiota: Insights from culture‐dependent and long‐read 16S rRNA gene sequencing methods
Letitia Grant, Manijeh Mohammadi Dehcheshmeh, Esmaeil Ebrahimie, Aliakbar Khabiri, Tania Veltman, Michael Shipstone, Darren J. Trott
Veterinary Dermatology.2025; 36(5): 581. CrossRef
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Zhili He, Wenfang Song, Shichang Zhang, Minlei Zhao, Fan Wang, Shanshan He, Xiaochi Jie, Qi Gao, Jianguo Chen
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Microbiota Modulation as an Approach to Prevent the Use of Antimicrobials Associated with Canine Atopic Dermatitis
Tânia Lagoa, Luís Martins, Maria Cristina Queiroga
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Oral Administration of Lactiplantibacillus plantarum KBL396 Regulates Serum 5-Hydroxytryptamine and Gut Microbiota: Evidence from a Preclinical Mouse Model and a Randomized Controlled Human Trial
Woojae Myung, Sung Jae Jang, Giljae Lee, Cheonghoon Lee, Kiuk Lee, Sung Hyun Moon, Yunsun Jeong, Woon-Ki Kim, SungJun Park, Hyungjin Lee, Yun Seong Park, Sangah Shin, Tae-Wook Nam, Hong Jin Jeon, GwangPyo Ko
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Environmental Adaptation of Psychrophilic Bacteria Subtercola spp. Isolated from Various Cryospheric Habitats: Hanbyul Lee , Yong-Joon Cho , Ahnna Cho , Ok-Sun Kim; J. Microbiol. 2023;61(7):663-672. Published online August 24, 2023; DOI: https://doi.org/10.1007/s12275-023-00068-y

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Abstract PDF: Subtercola boreus K300T is a novel psychrophilic strain that was isolated from permanently cold groundwater in Finland and has also been found in several places in Antarctica including lake, soil, and rocks. We performed genomic and transcriptomic analyses of 5 strains from Antarctica and a type strain to understand their adaptation to different environments. Interestingly, the isolates from rocks showed a low growth rate and smaller genome size than strains from the other isolation sources (lake, soil, and groundwater). Based on these habitat-dependent characteristics, the strains could be classified into two ecotypes, which showed differences in energy production, signal transduction, and transcription in the clusters of orthologous groups of proteins (COGs) functional category. In addition, expression pattern changes revealed differences in metabolic processes, including uric acid metabolism, DNA repair, major facilitator superfamily (MFS) transporters, and xylose degradation, depending on the nutritional status of their habitats. These findings provide crucial insights into the environmental adaptation of bacteria, highlighting genetic diversity and regulatory mechanisms that enable them to thrive in the cryosphere.

Heterologous Production and Structure Determination of a New Lanthipeptide Sinosporapeptin Using a Cryptic Gene Cluster in an Actinobacterium Sinosporangium siamense: Keita Saito , Keiichiro Mukai , Issara Kaweewan , Hiroyuki Nakagawa , Takeshi Hosaka , Shinya Kodani; J. Microbiol. 2023;61(6):641-648. Published online June 12, 2023; DOI: https://doi.org/10.1007/s12275-023-00059-z

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Lipolanthine is a subclass of lanthipeptide that has the modification of lipid moiety at the N-terminus. A cryptic biosynthetic gene cluster comprising four genes (sinA, sinKC, sinD, and sinE) involved in the biosynthesis of lipolanthine was identified in the genome of an actinobacterium Sinosporangium siamense. Heterologous coexpression of a precursor peptide coding gene sinA and lanthipeptide synthetase coding gene sinKC in the host Escherichia coli strain BL21(DE3) resulted in the synthesis of a new lanthipeptide, sinosporapeptin. It contained unusual amino acids, including one labionin and two dehydrobutyrine residues, as determined using NMR and MS analyses. Another coexpression experiment with two additional genes of decarboxylase (sinD) and N-acetyl transferase (sinE) resulted in the production of a lipolanthine-like modified sinosporapeptin.

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BGC heteroexpression strategy for production of novel microbial secondary metabolites
Yuanyuan Liu, Yuqi Tang, Zhiyang Fu, Wangjie Zhu, Hong Wang, Huawei Zhang
Metabolic Engineering.2025; 91: 1. CrossRef
Isolation and structure determination of a new antibacterial lanthipeptide derived from the marine derived bacterium Lysinibacillus sp.CTST325
Chanaphat Thetsana, Ryota Moriuchi, Shinya Kodani
World Journal of Microbiology and Biotechnology.2025;[Epub] CrossRef
Heterologous biosynthesis of myxobacterial lanthipeptides melittapeptins
Issara Kaweewan, Keiichiro Mukai, Pratchaya Rukthanapitak, Hiroyuki Nakagawa, Takeshi Hosaka, Shinya Kodani
Applied Microbiology and Biotechnology.2024;[Epub] CrossRef
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Youran Luo, Shuyun Xu, Autumn M. Frerk, Wilfred A. van der Donk
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Identification and Characterization of HEPN‑MNT Type II TA System from Methanothermobacter thermautotrophicus ΔH: Wonho Choi , Anoth Maharjan , Hae Gang Im , Ji-Young Park , Jong-Tae Park , Jung-Ho Park; J. Microbiol. 2023;61(4):411-421. Published online April 18, 2023; DOI: https://doi.org/10.1007/s12275-023-00041-9

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Toxin-antitoxin (TA) systems are widespread in bacteria and archaea plasmids and genomes to regulate DNA replication, gene transcr!ption, or protein translation. Higher eukaryotic and prokaryotic nucleotide-binding (HEPN) and minimal nucleotidyltransferase (MNT) domains are prevalent in prokaryotic genomes and constitute TA pairs. However, three gene pairs (MTH304/305, 408/409, and 463/464) of Methanothermobacter thermautotropicus ΔH HEPN-MNT family have not been studied as TA systems. Among these candidates, our study characterizes the MTH463/MTH464 TA system. MTH463 expression inhibited Escherichia coli growth, whereas MTH464 did not and blocked MTH463 instead. Using site-directed MTH463 mutagenesis, we determined that amino acids R99G, H104A, and Y106A from the R[ɸX]4-6H motif are involved with MTH463 cell toxicity. Furthermore, we established that purified MTH463 could degrade MS2 phage RNA, whereas purified MTH464 neutralized MTH463 activity in vitro. Our results indicate that the endonuclease toxin MTH463 (encoding a HEPN domain) and its cognate antitoxin MTH464 (encoding the MNT domain) may act as a type II TA system in M. thermautotropicus ΔH. This study provides initial and essential information studying TA system functions, primarily archaea HEPN-MNT family.

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Extensive Genomic Rearrangement of Catalase-Less Cyanobloom-Forming Microcystis aeruginosa in Freshwater Ecosystems
Minkyung Kim, Jaejoon Jung, Wonjae Kim, Yerim Park, Che Ok Jeon, Woojun Park
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Vibrio vulnificus PlpA facilitates necrotic host cell death induced by the pore forming MARTX toxin: Changyi Cho , Sanghyeon Choi , Myung Hee Kim , Byoung Sik Kim; J. Microbiol. 2022;60(2):224-233. Published online February 1, 2022; DOI: https://doi.org/10.1007/s12275-022-1448-x

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Opportunistic pathogen Vibrio vulnificus causes severe systemic infection in humans with high mortality. Although multiple exotoxins have been characterized in V. vulnificus, their interactions and potential synergistic roles in pathogen-induced host cell death have not been investigated previously. By employing a series of multiple exotoxin deletion mutants, we investigated whether specific exotoxins of the pathogen functioned together to achieve severe and rapid necrotic cell death. Human epithelial cells treated with V. vulnificus with a plpA deletion background exhibited an unusually prolonged cell blebbing, suggesting the importance of PlpA, a phospholipase A2, in rapid necrotic cell death by this pathogen. Additional deletion of the rtxA gene encoding the multifunctional autoprocessing repeats-in-toxin (MARTX) toxin did not result in necrotic cell blebs. However, if the rtxA gene was engineered to produce an effector-free MARTX toxin, the cell blebbing was observed, indicating that the pore forming activity of the MARTX toxin is sufficient, but the MARTX toxin effector domains are not necessary, for the blebbing. When a recombinant PlpA was treated on the blebbed cells, the blebs were completely disrupted. Consistent with this, MARTX toxin-pendent rapid release of cytosolic lactate dehydrogenase was significantly delayed in the plpA deletion background. Mutations in other exotoxins such as elastase, cytolysin/hemolysin, and/or extracellular metalloprotease did not affect the bleb formation or disruption. Together, these findings indicate that the pore forming MARTX toxin and the phospholipase A2, PlpA, cooperate sequentially to achieve rapid necrotic cell death by inducing cell blebbing and disrupting the blebs, respectively.

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Vagococcus zengguangii sp. nov., isolated from yak faeces: Yajun Ge , Dong Jin , Xin-He Lai , Jing Yang , Shan Lu , Ying Huang , Han Zheng , Xiaoyan Zhang , Jianguo Xu; J. Microbiol. 2021;59(1):1-9. Published online December 23, 2020; DOI: https://doi.org/10.1007/s12275-021-0406-3

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Two unknown Gram-stain-positive, catalase- and oxidasenegative, non-motile, and coccus-shaped bacteria, designated MN-17T and MN-09, were isolated from yaks faeces (Bos grunniens) in the Qinghai-Tibet Plateau of China. 16S rRNA gene sequence-based comparative analyses revealed that the two strains were grouped within the genus Vagococcus, displaying the highest similarity with Vagococcus xieshaowenii CGMCC 1.16436T (98.6%) and Vagococcus elongatus CCUG 51432T (96.4%). Both strains grew optimally at 37°C and pH 7.0 in the presence of 0.5% (w/v) NaCl. The complete genome of MN-17T comprises 2,085 putative genes with a total of 2,190,262 bp and an average G + C content of 36.7 mol%. The major fatty acids were C16:0 (31.2%), C14:0 (28.5%), and C18:1ω9c (13.0%); the predominant respiratory quinone was MK-7 (68.8%); the peptidoglycan type was A4α(L-Lys-DAsp); and the major polar lipid was diphosphatidylglycerol. Together, these supported the affiliation of strain MN-17T to the genus Vagococcus. In silico DNA-DNA hybridization and the average nucleotide identity values between MN-17T and all recognized species in the genus were 21.6–26.1% and 70.7–83.0%, respectively. MN-17T produced acid from D-cellobiose, D-fructose, glycerol, D-glucose, N-acetyl-glucosamine, gentiobiose, D-mannose, D-maltose, D-ribose, Dsaccharose, salicin, D-trehalose, and D-xylose. These results distinguished MN-17T and MN-09 from closely related species in Vagococcus. Thus, we propose that strains MN-17T and MN-09 represent a novel species in the genus Vagococcus, with the name Vagococcus zengguangii sp. The type strain is MN-17T (= CGMCC 1.16726T = GDMCC 1.1589T = JCM 33478T).

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Vagococcus proximus sp. nov. and Vagococcus intermedius sp. nov., originating from modified atmosphere packaged broiler meat
Per Johansson, Elina Jääskeläinen, Elina Säde, Johanna Björkroth
International Journal of Systematic and Evolutionary Microbiology .2023;[Epub] CrossRef
Phenotypic and genomic characteristics of Brevibacterium zhoupengii sp. nov., a novel halotolerant actinomycete isolated from bat feces
Yuyuan Huang, Lingzhi Dong, Jian Gong, Jing Yang, Shan Lu, Xin-He Lai, Dong Jin, Qianni Huang, Ji Pu, Liyun Liu, Jianguo Xu
Journal of Microbiology.2022; 60(10): 977. CrossRef

Analyses of DNA double-strand break repair pathways in tandem arrays of HXT genes of Saccharomyces cerevisiae: Ju-Hee Choi , Ye-Seul Lim , Min-Ku Kim , Sung-Ho Bae; J. Microbiol. 2020;58(11):957-966. Published online October 30, 2020; DOI: https://doi.org/10.1007/s12275-020-0461-1

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Eukaryotic genomes contain numerous homologous repeat sequences including redundant genes with divergent homology that can be potential recombination targets. Recombination between divergent sequences is rare but poses a substantial threat to genome stability. The hexose transporter (HXT) gene family shares high sequence similarities at both protein and DNA levels, and some members are placed close together in tandem arrays. In this study, we show that spontaneous interstitial deletions occur at significantly high rates in HXT gene clusters, resulting in chimeric HXT sequences that contain a single junction point. We also observed that DNA double-strand breaks created between HXT genes produce primarily interstitial deletions, whereas internal cleavage of the HXT gene resulted in gene conversions as well as deletion products. Interestingly, interstitial deletions were less constrained by sequence divergence than gene conversion. Moreover, recombination-defective mutations differentially affected the survival frequency. Mutations that impair single-strand annealing (SSA) pathway greatly reduced the survival frequency by 10–1,000-fold, whereas disruption of Rad51-dependent homologous recombination exhibited only modest reduction. Our results indicate that recombination in the tandemly repeated HXT genes occurs primarily via SSA pathway.

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Ju-Hee Choi, Oyungoo Bayarmagnai, Sung-Ho Bae
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Jucan Gao, Cuifang Ye, Jintao Cheng, Lihong Jiang, Xinghao Yuan, Jiazhang Lian
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Effects of the loss of mismatch repair genes on single-strand annealing between divergent sequences in Saccharomyces cerevisiae
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Journal of Microbiology.2021; 59(4): 401. CrossRef

Iron interferes with quorum sensing-mediated cooperation in Pseudomonas aeruginosa by affecting the expression of ppyR and mexT, in addition to rhlR: Feng Sun , Na Li , Lijia Wang , Huajun Feng , Dongsheng Shen , Meizhen Wang; J. Microbiol. 2020;58(11):938-944. Published online October 30, 2020; DOI: https://doi.org/10.1007/s12275-020-0264-4

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The stabilization of quorum sensing (QS) is vital for bacterial survival in various environments. Although the mechanisms of QS stabilization in certain conditions have been well studied, the impact of environmental factors has received much less attention. In this study, we show that the supplementation of 25 μM iron in competition experiments and 50 μM in evolution experiments to casein growth cultures significantly increased the possibility of population collapse by affecting elastase production. However, the expression of lasI and lasR remained constant regardless of iron concentration and hence this effect was not through interference with the LasIR circuit, which mainly regulates the secretion of elastase in Pseudomonas aeruginosa. However, the expression of rhlR was significantly inhibited by iron treatment, which could affect the production of elastase. Further, based on both reverse transcription quantitative polymerase chain reaction and gene knock-out assays, we show that iron inhibits the transcription of ppyR and enhances the expression of mexT, both of which decrease elastase production and correspondingly interfere with QS stabilization. Our findings show that environmental factors can affect the genes of QS circuits, interfering with QS stabilization. These findings are not only beneficial in understanding the mechanistic effect of iron on QS stabilization, but also demonstrate the complexity of QS stabilization by linking non-QS-related genes with QS traits.

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Anti-inflammatory and anti-oxidative effect of Korean propolis on Helicobacter pylori-induced gastric damage in vitro: Moon-Young Song , Da-Young Lee , Eun-Hee Kim; J. Microbiol. 2020;58(10):878-885. Published online September 2, 2020; DOI: https://doi.org/10.1007/s12275-020-0277-z

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Helicobacter pylori, present in the stomach lining, is a Gramnegative bacterium that causes various gastrointestinal diseases, including gastritis and peptic ulcers. Propolis is a natural resinous substance collected from a variety of plants, and contains several natural bioactive substances. The aim of this study was to investigate the anti-inflammatory and antioxidative effects of Korean propolis on H. pylori-induced damage in the human adenocarcinoma gastric cell line. The propolis used in this study was obtained from the Korea Beekeeping Association in South Korea. The expression of pro-inflammatory interleukins (ILs), such as IL-8, IL-12, IL-1β, tumor necrosis factor alpha, cyclooxygenase-2, and inducible nitric oxide synthase, which was increased after H. pylori infection, significantly decreased in a dose-dependent manner upon pretreatment with Korean propolis, because of the suppression of mitogen-activated protein kinases and nuclear factor κB pathway. The anti-oxidative activity of propolis was assessed using the 2,2-diphenyl-1-picrylhydrazyl hydrate free radical assay. Korean propolis showed significant anti-oxidative effects via reactive oxygen species scavenging. In addition, pretreatment with Korean propolis upregulated the expression of anti-oxidant enzymes through Nrf2 signaling activation. These findings indicate that the use of Korean propolis, which has anti-inflammatory and anti-oxidative effects, can be promising for the prevention of H. pylori-induced gastric damage.

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Caspase-3 inhibitor inhibits enterovirus D68 production: Wenbo Huo , Jinghua Yu , Chunyu Liu , Ting Wu , Yue Wang , Xiangling Meng , Fengmei Song , Shuxia Zhang , Ying Su , Yumeng Liu , Jinming Liu , Xiaoyan Yu , Shucheng Hua; J. Microbiol. 2020;58(9):812-820. Published online September 1, 2020; DOI: https://doi.org/10.1007/s12275-020-0241-y

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Enterovirus D68 (EVD68) is an emerging pathogen that recently caused a large worldwide outbreak of severe respiratory disease in children. However, the relationship between EVD68 and host cells remains unclear. Caspases are involved in cell death, immune response, and even viral production. We found that caspase-3 was activated during EVD68 replication to induce apoptosis. Caspase-3 inhibitor (Z-DEVDFMK) inhibited viral production, protected host cells from the cytopathic effects of EVD68 infection, and prevented EVD68 from regulating the host cell cycle at G0/G1. Meanwhile, caspase-3 activator (PAC-1) increased EVD68 production. EVD68 infection therefore activates caspase-3 for virus production. This knowledge provides a potential direction for the prevention and treatment of disease related to EVD68.

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Simultaneous detection of Salmonella spp., Pseudomonas aeruginosa, Bacillus cereus, and Escherichia coli O157:H7 in environmental water using PMA combined with mPCR: Guoyang Xie , Shuang Yu , Wen Li , Dan Mu , Zoraida P. Aguilar , Hengyi Xu; J. Microbiol. 2020;58(8):668-674. Published online June 25, 2020; DOI: https://doi.org/10.1007/s12275-020-0084-6

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A multiplex polymerase chain reaction (mPCR) with propidium monoazide (PMA) and internal amplification control (IAC) for the simultaneous detection of waterborne pathogens Salmonella spp., Pseudomonas aeruginosa, Bacillus cereus, and Escherichia coli O157:H7, was developed. This PMA-IAC-mPCR assay used four new specific primers based on the genes for invA, ecfX, cesB, and fliC, respectively. A 16S rRNA primer was chosen for IAC to eliminate false negative
results
. The photosensitive dye, propidium monoazide (PMA) was used to exclude signals from dead bacteria that could lead to false positive results. In pure culture, the limits of detection (LOD) were 101 CFU/ml for P. aeruginosa, 102 CFU/ml for both Salmonella spp. and E. coli O157:H7, and 103 CFU/ml for B. cereus, respectively. In addition, with a 6–8 h enrichment of all four bacteria that were combined in a mixture that was spiked in water sample matrix, the LOD was 3 CFU/ml for Salmonella spp., 7 CFU/ml for E. coli O157:H7, 10 CFU/ml for B. cereus and 2 CFU/ml for P. aeruginosa. This PMA-IAC-mPCR assay holds potential for application in the multiplex assay of waterborne pathogens.

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Endophytic bacterial and fungal microbiota in different cultivars of cassava (Manihot esculenta Crantz): Hong Li , Chengliang Yan , Yanqiong Tang , Xiang Ma , Yinhua Chen , Songbi Chen , Min Lin , Zhu Liu; J. Microbiol. 2020;58(7):614-623. Published online May 18, 2020; DOI: https://doi.org/10.1007/s12275-020-9565-x

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Endophytes colonize tissues of healthy host plants and play a crucial role in plant growth and development. However, little attention has been paid to the endophytes of tuber crops such as cassava, which is used as a staple food by approximately 800 million people worldwide. This study aimed to elucidate the diversity and composition of endophytic bacterial and fungal communities in different cassava cultivars using high-throughput sequencing. Although no significant differences in richness or diversity were observed among the different cassava cultivars, the community compositions were diverse. Two cultivars (SC124 and SC205) tolerant to root rot exhibited similar community compositions, while two other cultivars (SC10 and SC5), which are moderately and highly susceptible to root rot, respectively, harboured similar community compositions. Proteobacteria, Firmicutes, and Ascomycota dominated the endophyte assemblages, with Weissella, Serratia, Lasiodiplodia, Fusarium, and Diaporthe being the predominant genera. The differentially abundant taxonomic clades between the tolerant and susceptible cultivars were mainly rare taxa, such as Lachnoclostridium_5, Rhizobium, Lampropedia, and Stenotrophomonas. These seemed to be key genera that affected the susceptibility of cassava to root rot. Moreover, the comparison of KEGG functional profiles revealed that ‘Environmental adaptation’ category was significantly enriched in the tolerant cultivars, while ‘Infectious diseases: Parasitic’ category was significantly enriched in the susceptible cultivars. The present findings open opportunities for further studies on the roles of endophytes in the susceptibility of plants to diseases.

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Effective mucosal live attenuated Salmonella vaccine by deleting phosphotransferase system component genes ptsI and crr: Yong Zhi , Shun Mei Lin , A-Yeung Jang , Ki Bum Ahn , Hyun Jung Ji , Hui-Chen Guo , Sangyong Lim , Ho Seong Seo; J. Microbiol. 2019;57(1):64-73. Published online October 2, 2018; DOI: https://doi.org/10.1007/s12275-019-8416-0

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Salmonella enterica is a major human pathogen that causes invasive non-typhoidal Salmonellosis (iNTS), resulting in significant morbidity and mortality. Although a number of pre-clinical and clinical studies have reported on the feasibility of developing a safe and effective vaccine against iNTS, there have been no licensed Salmonella vaccines available to protect against NTS strains. Vaccine formulations of highest priority for NTS are live attenuated vaccines, which can elicit effective induction of intestinal mucosal and intracellular bacteria-specific cell mediated immune responses. Since glucose is crucial for intracellular survival and replication in host cells, we constructed strains with mutations in components of the glucose uptake system, called the phosphotransferase system (PTS), and compared the relative virulence and immune responses in mice. In this study, we found that the strain with mutations in both ptsI and crr (KST0556) was the most attenuated strain among the tested strains, and proved to be highly effective in inducing a mucosal immune response that can protect against NTS infections in mice. Thus, we suggest here that KST0556 (ΔptsIΔcrr) is a potential live vaccine candidate for NTS, and may also be a candidate for a live delivery vector for heterologous antigens. Moreover, since PTS is a well-conserved glucose transporter system in both Gramnegative and Gram-positive bacteria, the ptsI and crr genes may be potential targets for creating live bacterial vectors or vaccine strains.

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Gamma-irradiation of Streptococcus pneumoniae for the use as an immunogenic whole cell vaccine: Min Yong Jwa , Soyoung Jeong , Eun Byeol Ko , A Reum Kim , Hyun Young Kim , Sun Kyung Kim , Ho Seong Seo , Cheol-Heui Yun , Seung Hyun Han; J. Microbiol. 2018;56(8):579-585. Published online July 25, 2018; DOI: https://doi.org/10.1007/s12275-018-8347-1

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Streptococcus pneumoniae is a major respiratory pathogen that causes millions of deaths worldwide. Although subunit vaccines formulated with the capsular polysaccharides or their protein conjugates are currently-available, low-cost vaccines with wide serotype coverage still remain to be developed, especially for developing countries. Recently, gamma- irradiation has been considered as an effective inactivation
method
to prepare S. pneumoniae vaccine candidate. In this study, we investigated the immunogenicity and protective immunity of gamma-irradiated S. pneumoniae (r-SP), by comparing with heat-inactivated S. pneumoniae (h-SP) and formalin-inactivated S. pneumoniae (f-SP), both of which were made by traditional inactivation methods. Intranasal immunization of C57BL/6 mice with r-SP in combination with cholera toxin as an adjuvant enhanced S. pneumoniaespecific antibodies on the airway mucosal surface and in sera more potently than that with h-SP or f-SP under the same conditions. In addition, sera from mice immunized with r- SP potently induced opsonophagocytic killing activity more effectively than those of h-SP or f-SP, implying that r-SP could induce protective antibodies. Above all, immunization with r-SP effectively protected mice against S. pneumoniae infection. Collectively, these results suggest that gamma- irradiation is an effective method for the development of a killed whole cell pneumococcal vaccine that elicits robust mucosal and systemic immune responses.

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Analysis of IE62 mutations found in Varicella-Zoster virus vaccine strains for transactivation activity: Hyemin Ko , Gwang Myeong Lee , Ok Sarah Shin , Moon Jung Song , Chan Hee Lee , Young Eui Kim , Jin-Hyun Ahn; J. Microbiol. 2018;56(6):441-448. Published online June 1, 2018; DOI: https://doi.org/10.1007/s12275-018-8144-x

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Live attenuated vaccine strains have been developed for Varicella- Zoster virus (VZV). Compared to clinically isolated strains, the vaccine strains contain several non-synonymous mutations in open reading frames (ORFs) 0, 6, 31, 39, 55, 62, and 64. In particular, ORF62, encoding an immediate-early (IE) 62 protein that acts as a transactivator for viral gene expression, contains six non-synonymous mutations, but whether these mutations affect transactivation activity of IE62 is not understood. In this study, we investigated the role of non-synonymous vaccine-type mutations (M99T, S628G, R958G, V1197A, I1260V, and L1275S) of IE62 in Suduvax, a vaccine strain isolated in Korea, for transactivation activity. In reporter assays, Suduvax IE62 showed 2- to 4-fold lower transactivation activity toward ORF4, ORF28, ORF29, and ORF68 promoters than wild-type IE62. Introduction of individual M99T, S628G, R958G, or V1197A/ I1260V/L1275S mutations into wild-type IE62 did not affect transactivation activity. However, the combination of M99T within the N-terminal Sp transcription factor binding region and V1197A/I1260V/L1275S within the C-terminal serineenriched acidic domain (SEAD) significantly reduced the transactivation activity of IE62. The M99T/V1197A/I1260V/ L1275S mutant IE62 did not show considerable alterations in intracellular distribution and Sp3 binding compared to wild-type IE62, suggesting that other alteration(s) may be responsible for the reduced transactivation activity. Collectively, our results suggest that acquisition of mutations in both Met 99 and the SEAD of IE62 is responsible for the reduced transactivation activity found in IE62 of the VZV vaccine strains and contributes to attenuation of the virus.

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Heightened incidence of adverse events associated with a live attenuated varicella vaccine strain that lacks critical genetic polymorphisms in open reading frame 62
Ye Ji Kim, Doyeop Oh, Jaehoon Kim, Jeongtae Son, Jae Yun Moon, Ye Kyung Kim, Bin Ahn, Kyu Ri Kang, Daechan Park, Hyun Mi Kang
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Soo-Jin Oh, Sooyeon Lim, Moon Jung Song, Jin Hyun Ahn, Chan Hee Lee, Ok Sarah Shin
Pathogens.2019; 8(4): 183. CrossRef

Guinea pig complement potently measures vibriocidal activity of human antibodies in response to cholera vaccines: Kyoung Whun Kim , Soyoung Jeong , Ki Bum Ahn , Jae Seung Yang , Cheol-Heui Yun , Seung Hyun Han; J. Microbiol. 2017;55(12):973-978. Published online December 7, 2017; DOI: https://doi.org/10.1007/s12275-017-7478-0

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The vibriocidal assay using guinea pig complement is widely used for the evaluation of immune responses to cholera vaccines in human clinical trials. However, it is unclear why guinea pig complement has been used over human complement in the measurement of vibriocidal activity of human sera and there have not been comparison studies for the use of guinea pig complement over those from other species. Therefore, we comparatively investigated the effects of complements derived from human, guinea pig, rabbit, and sheep on vibriocidal activity. Complements from guinea pig, rabbit, and human showed concentration-dependent vibriocidal activity in the presence of quality control serum antibodies. Of these complements, guinea pig complement was the most sensitive and effective over a wide concentration range. When the vibriocidal activity of complements was measured in the absence of serum antibodies, human, sheep, and guinea pig complements showed vibriocidal activity up to 40-fold, 20- fold, and 1-fold dilution, respectively. For human pre- and post-vaccination sera, the most potent vibriocidal activity was observed when guinea pig complement was used. In addition, the highest fold-increases between pre- and post- vaccinated sera were obtained with guinea pig complement. Furthermore, human complement contained a higher amount of V. cholerae- and its lipopolysaccharide-specific antibodies than guinea pig complement. Collectively, these results suggest that guinea pig complements are suitable for vibriocidal assays due to their high sensitivity and effectiveness to human sera.

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Immunogenicity and protective efficacy of a live, oral cholera vaccine formulation stored outside-the-cold-chain for 140 days
Tew Hui Xian, Kurunathan Sinniah, Chan Yean Yean, Venkateskumar Krishnamoorthy, Mohd Baidi Bahari, Manickam Ravichandran, Guruswamy Prabhakaran
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A high-throughput, bead-based, antigen-specific assay to assess the ability of antibodies to induce complement activation
Stephanie Fischinger, Jonathan K. Fallon, Ashlin R. Michell, Thomas Broge, Todd J. Suscovich, Hendrik Streeck, Galit Alter
Journal of Immunological Methods.2019; 473: 112630. CrossRef
Characterization of antibody response in patients with acute and chronic chikungunya virus disease
Fatih Anfasa, Stephanie M. Lim, Susan Fekken, Robert Wever, Albert D.M.E. Osterhaus, Byron E.E. Martina
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Recombinant baculovirus-based vaccine expressing M2 protein induces protective CD8+ T-cell immunity against respiratory syncytial virus infection: Jeong-Yoon Lee , Jun Chang; J. Microbiol. 2017;55(11):900-908. Published online October 27, 2017; DOI: https://doi.org/10.1007/s12275-017-7306-6

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Respiratory syncytial virus (RSV) is an important cause of acute lower respiratory tract disease in infants, young children, immunocompromised individuals, and the elderly. However, despite ongoing efforts to develop an RSV vaccine, there is still no authorized RSV vaccine for humans. Baculovirus has attracted attention as a vaccine vector because of its ability to induce a high level of humoral and cellular immunity, low cytotoxicity against various antigens, and biological safety for humans. In this study, we constructed a recombinant baculovirus- based vaccine expressing the M2 protein of RSV under the control of cytomegalovirus promoter (Bac_RSVM2) to induce CD8+ T-cell responses which play an important role in viral clearance, and investigated its protective efficacy against RSV infection. Immunization with Bac_RSVM2 via intranasal or intramuscular route effectively elicited the specific CD8+ T-cell responses. Most notably, immunization with Bac_RSVM2 vaccine almost completely protected mice from RSV challenge without vaccine-enhanced immunopathology. In conclusion, these results suggest that Bac_RSVM2 vaccine employing the baculovirus delivery platform has promising potential to be developed as a safe and novel RSV vaccine that provides protection against RSV infection.

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Heterologous prime-boost immunization with live SPY1 and DnaJ protein of Streptococcus pneumoniae induces strong Th1 and Th17 cellular immune responses in mice: Yulan Qiu , Xuemei Zhang , Xinyuan Zhang , Yunjun Mo , Xiaoyu Sun , Jichao Wang , Yibing Yin , Wenchun Xu; J. Microbiol. 2017;55(10):823-829. Published online September 28, 2017; DOI: https://doi.org/10.1007/s12275-017-7262-1

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Abstract PDF

diseases in children under 5-year-old. Vaccine has been used as an indispensable strategy to prevent S. pneumoniae infection for more than 30 years. Our previous studies confirmed that mucosal immunization with live attenuated strain SPY1 can protect mice against nasopharyngeal colonization of S. pneumoniae and lethal pneumococcal infection, and the protective effects are comparable with those induced by commercially available 23-valent polysaccharide vaccine. However, live attenuated vaccine SPY1 needs four inoculations to get satisfactory protective effect, which may increase the risk of virulence recovery. It is reported that heterologous primeboost approach is more effective than homologous primeboost approach. In the present study, to decrease the doses of live SPY1 and improve the safety of SPY1 vaccine, we immunized mice with SPY1 and DnaJ protein alternately. Our
results
showed that heterologous prime-boost immunization with SPY1 and DnaJ protein could significantly reduce the colonization of S. pneumoniae in the respiratory tract of mice, and induce stronger Th1 and Th17 cellular immune responses than SPY1 alone. These results indicate heterologous prime-boost immunization method not only elicits better protective effect than SPY1 alone, but also reduces the doses of live SPY1 and decreases the risk of SPY1 vaccine. This work is the first time to study the protective efficiency with two different forms of S. pneumoniae candidate vaccine, and provides a new strategy for the development of S. pneumoniae vaccine.

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Reviews

REVIEW] H5 influenza, a global update: Rhodri Harfoot , Richard J. Webby; J. Microbiol. 2017;55(3):196-203. Published online February 28, 2017; DOI: https://doi.org/10.1007/s12275-017-7062-7

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H5 influenza viruses have caused much alarm globally due to their high pathogenic potential. As yet we have not seen sustained spread of the virus amongst humans despite a high prevalence of the virus in avian populations. Nevertheless, isolated human cases of infection have demonstrated high mortality and there are substantial efforts being taken to monitor the evolution of the virus and to undertake preparedness activities. Here we review and discuss the evolution of the A/goose/Guangdong/1/96 (H5N1) virus with emphasis on recent events.

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REVIEW] Exploiting virus-like particles as innovative vaccines against emerging viral infections: Hotcherl Jeong , Baik Lin Seong; J. Microbiol. 2017;55(3):220-230. Published online February 28, 2017; DOI: https://doi.org/10.1007/s12275-017-7058-3

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Abstract PDF

Emerging viruses pose a major threat to humans and livestock with global public health and economic burdens. Vaccination remains an effective tool to reduce this threat, and yet, the conventional cell culture often fails to produce sufficient vaccine dose. As an alternative to cell-culture based vaccine, virus-like particles (VLPs) are considered as a highpriority vaccine strategy against emerging viruses. VLPs represent highly ordered repetitive structures via macromolecular assemblies of viral proteins. The particulate nature allows efficient uptake into antigen presenting cells stimulating both innate and adaptive immune responses towards enhanced vaccine efficacy. Increasing research activity and translation opportunity necessitate the advances in the design of VLPs and new bioprocessing modalities for efficient and cost-effective production. Herein, we describe major achievements and challenges in this endeavor, with respect to designing strategies to harnessing the immunogenic potential, production platforms, downstream processes, and some exemplary
case
s in developing VLP-based vaccines.

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REVIEW] Modulation of the host immune response by respiratory syncytial virus proteins: Megan E. Schmidt , Steven M. Varga; J. Microbiol. 2017;55(3):161-171. Published online February 28, 2017; DOI: https://doi.org/10.1007/s12275-017-7045-8

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Respiratory syncytial virus (RSV) causes severe respiratory disease in both the very young and the elderly. Nearly all individuals become infected in early childhood, and reinfections with the virus are common throughout life. Despite its clinical impact, there remains no licensed RSV vaccine. RSV infection in the respiratory tract induces an inflammatory response by the host to facilitate efficient clearance of the virus. However, the host immune response also contributes to the respiratory disease observed following an RSV infection. RSV has evolved several mechanisms to evade the host immune response and promote virus replication through interactions between RSV proteins and immune components. In contrast, some RSV proteins also play critical roles in activating, rather than suppressing, host immunity. In this review, we discuss the interactions between individual RSV proteins and host factors that modulate the immune response and the implications of these interactions for the course of an RSV infection.

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MINIREVIEW] Advances in novel influenza vaccines: a patent review: Jae-Min Song; J. Microbiol. 2016;54(6):403-412. Published online May 27, 2016; DOI: https://doi.org/10.1007/s12275-016-6176-7

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The threat of a major human influenza pandemic such as the avian H5N1 or the 2009 new H1N1 has emphasized the need for effective prevention strategies to combat these pathogens. Although egg based influenza vaccines have been well established for a long time, it remains an ongoing public health need to develop alternative production methods that ensures improved safety, efficacy, and ease of administration compared with conventional influenza vaccines. This article is intended to cover some of the recent advances and related patents on the development of influenza vaccines including live attenuated, cell based, genomic and synthetic peptide vaccines.

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Research Support, Non-U.S. Gov'ts

Therapeutic potential of an AcHERV-HPV L1 DNA vaccine: Hee-Jung Lee , Jong Kwang Yoon , Yoonki Heo , Hansam Cho , Yeondong Cho , Yongdae Gwon , Kang Chang Kim , Jiwon Choi , Jae Sung Lee , Yu-Kyoung Oh , Young Bong Kim; J. Microbiol. 2015;53(6):415-420. Published online May 30, 2015; DOI: https://doi.org/10.1007/s12275-015-5150-0

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Cervical cancer is strongly associated with chronic human papillomavirus infections, among which HPV16 is the most common. Two commercial HPV vaccines, Gardasil and Cervarix are effective for preventing HPV infection, but cannot be used to treat existing HPV infections. Previously, we developed a human endogenous retrovirus (HERV)-enveloped recombinant baculovirus capable of delivering the L1 genes of HPV types 16, 18, and 58 (AcHERV-HP16/18/58L1, AcHERV-HPV). Intramuscular administration of AcHERVHPV vaccines induced a strong cellular immune response as well as a humoral immune response. In this study, to examine the therapeutic effect of AcHERV-HPV in a mouse model, we established an HPV16 L1 expressing tumor cell line. Compared to Cervarix, immunization with AcHERVHPV greatly enhanced HPV16 L1-specific cytotoxic T lymphocytes (CTL) in C57BL/6 mice. Although vaccination could not remove preexisting tumors, strong CTL activity retarded the growth of inoculated tumor cells. These results indicate that AcHERV-HPV could serve as a potential therapeutic DNA vaccine against concurrent infection with HPV 16, 18, and 58.

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Preliminary Study about Sublingual Administration of Bacteria-expressed Pandemic H1N1 Influenza Vaccine in Miniature Pigs: Hyekwon Kim , Jeong-Ki Kim , Hohyun Song , Jungah Choi , Byoungshik Shim , Bokyu Kang , Hyoungjoon Moon , Minjoo Yeom , Sang-Hyun Kim , Daesub Song , Manki Song; J. Microbiol. 2014;52(9):794-800. Published online July 30, 2014; DOI: https://doi.org/10.1007/s12275-014-4289-4

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Abstract PDF

Sublingual (SL) administration of influenza vaccine would be non-invasive and effective way to give human populations protective immunity against the virus, especially when pandemic influenza outbreaks. In this study, the efficacy of pandemic influenza virus-based subunit vaccines was tested after sublingual (SL) adjuvant administration in pigs. Eight specific pathogen-free Yucatan pigs were divided into 4 groups: nonvaccinated but challenged (A) and vaccinated and challenged (B, C, and D). The vaccinated groups were subdivided by vaccine type and inoculation route: SL subunit vaccine (hemagglutinin antigen 1 [HA1] + wild-type cholera toxin [wtCT], B); IM subunit vaccine (HA1 + aluminum hydroxide, C); and IM inactivated vaccine (+ aluminum hydroxide, D). The vaccines were administered twice at a 2-week interval. All pigs were challenged with pandemic influenza virus (A/swine/ GCVP-KS01/2009 [H1N1]) and monitored for clinical signs, serology, viral shedding, and histopathology. After vaccination, hemagglutination inhibition titre was higher in group D (320) than in the other vaccinated groups (40–80) at the time of challenge. The mobility and feed intake were reduced in group C. Both viral shedding and histopathological lesions were reduced in groups B and D. Although this study has limitation due to the limited number of pigs (2 pigs per a group), the preliminary data in this study provided the protective potential of SL administration of bacteria-expressed pandemic H1N1 influenza vaccine in pigs. There should be additional animal studies about effective adjuvant system and vaccine types for the use of SL influenza vaccination.

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A Potent Brucella abortus 2308 Δery Live Vaccine Allows for the Differentiation between Natural and Vaccinated Infection: Junbo Zhang , Shuanghong Yin , Fei Guo , Ren Meng , Chuangfu Chen , Hui Zhang , Zhiqiang Li , Qiang Fu , Huijun Shi , Shengwei Hu , Wei Ni , Tiansen Li , Ke Zhang; J. Microbiol. 2014;52(8):681-688. Published online July 4, 2014; DOI: https://doi.org/10.1007/s12275-014-3689-9

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Abstract PDF

Brucellosis is a globally distributed zoonotic disease that causes animal and human diseases. However, the current Brucella abortus vaccines (S19 and RB51) are deficient; they can cause abortion in pregnant animals. Moreover, when the vaccine S19 is used, tests cannot differentiate natural from vaccinated infection. Therefore, a safer and more potent vaccine is needed. A Brucella abortus 2308 ery promoter mutant (Δery) was constructed to overcome these drawbacks. The growth of the Δery mutant was significantly attenuated in macrophages and mice and induced high protective immunity in mice. Moreover, Δery induced an anti-Brucellaspecific IgG (immunoglobulin G) response and stimulated the expression of interferon-gamma (INF-γ) and interleukin-4 (IL-4). Furthermore, the expression of EryA antigen allowed for the serological differentiation between natural and vaccinated infection in mice. These results indicate that the Δery mutant is a potential attenuated live vaccine candidate against virulent Brucella abortus 2308 (S2308) infection.

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Expression and regulation of the ery operon of Brucella melitensis in human trophoblast cells
Hui Zhang, Xiaoxia Dou, Zhiqiang Li, Yu Zhang, Jing Zhang, Fei Guo, Yuanzhi Wang, Zhen Wang, Tiansen Li, Xinli Gu, Chuangfu Chen
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Protection efficacy of the Brucella abortus ghost vaccine candidate lysed by the N-terminal 24-amino acid fragment (GI24) of the 36-amino acid peptide PMAP-36 (porcine myeloid antimicrobial peptide 36) in murine models
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The Brucella melitensis M5-90 phosphoglucomutase (PGM) mutant is attenuated and confers protection against wild-type challenge in BALB/c mice
Yu Zhang, Tiansen Li, Jing Zhang, Zhiqiang Li, Yan Zhang, Zhen Wang, Hanping Feng, Yuanzhi Wang, Chuangfu Chen, Hui Zhang
World Journal of Microbiology and Biotechnology.2016;[Epub] CrossRef
A Brucella melitensis M5-90 wboA deletion strain is attenuated and enhances vaccine efficacy
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Development of a Chimeric Strain of Porcine Reproductive and Respiratory Syndrome Virus with an Infectious Clone and a Korean Dominant Field Strain: Jung-Ah Lee , Nak-Hyung Lee , Sang-Won Lee , Seung-Yong Park , Chang-Seon Song , In-Soo Choi , Joong-Bok Lee; J. Microbiol. 2014;52(4):345-349. Published online March 29, 2014; DOI: https://doi.org/10.1007/s12275-014-4074-4

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Abstract PDF

The K418 chimeric virus of porcine reproductive and respiratory syndrome virus (PRRSV) was engineered by replacing the genomic region containing structure protein genes of an infectious clone of PRRSV, FL12, with the same region obtained from a Korean dominant field strain, LMY. The K418 reached 106 TCID50/ml of viral titer with similar growth kinetics to those of parental strains and had a cross-reactive neutralizing antibody response to field serum from the entire country. The chimeric clone pK418 can be used as a practical tool for further studying the molecular characteristics of PRRSV proteins through genetic manipulation. Furthermore, successful construction of the K418 will allow for the development of customized vaccine candidates against PRRSV, which has evolved rapidly in Korea.

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Serotype-Independent Protection against Pneumococcal Infections Elicited by Intranasal Immunization with Ethanol-Killed Pneumococcal Strain, SPY1: Xiuyu Xu , Jiangping Meng , Yiping Wang , Jie Zheng , Kaifeng Wu , Xuemei Zhang , Yibing Yin , Qun Zhang; J. Microbiol. 2014;52(4):315-323. Published online March 29, 2014; DOI: https://doi.org/10.1007/s12275-014-3583-5

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Abstract PDF

The 23-valent polysaccharide vaccine and the 7-valent pneumococcal conjugate vaccine are licensed vaccines that protect against pneumococcal infections worldwide. However, the incidence of pneumococcal diseases remains high in lowincome countries. Whole-cell vaccines with high safety and strong immunogenicity may be a favorable choice. We previously obtained a capsule-deficient Streptococcus pneumoniae mutant named SPY1 derived from strain D39. As an attenuated live pneumococcal vaccine, intranasal immunization with SPY1 elicits broad serotype-independent protection against pneumococcal infection. In this study, for safety consideration, we inactivated SPY1 with 70% ethanol and intranasally immunized BALB/c mice with killed SPY1 plus cholera toxin adjuvant for four times. Results showed that intranasal immunization with inactivated SPY1 induced strong humoral and cellular immune responses. Intranasal immunization with inactivated SPY1 plus cholera toxin adjuvant elicited effective serotype-independent protection against the colonization of pneumococcal strains 19F and 4 as well as lethal infection of pneumococcal serotypes 2, 3, 14, and 6B. The protection rates provided by inactivated SPY1 against lethal pneumococcal infection were comparable to those of currently used polysaccharide vaccines. In addition, vaccinespecific B-cell and T-cell immune responses mediated the protection elicited by SPY1. In conclusion, the 70% ethanolinactivated pneumococcal whole-cell vaccine SPY1 is a potentially safe and less complex vaccine strategy that offers broad protection against S. pneumoniae.

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Streptococcus pneumoniae serotype distribution in low- and middle-income countries of South Asia: Do we need to revisit the pneumococcal vaccine strategy?
Priya Dhawale, Sanket Shah, Kaushal Sharma, Deepa Sikriwal, Varnik Kumar, Arnabjyoti Bhagawati, Sakshi Dhar, Pratiksha Shetty, Syed Ahmed
Human Vaccines & Immunotherapeutics.2025;[Epub] CrossRef
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Corrected and Republished from: “A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against LethalStreptococcus pneumoniaeChallenge”
Win-Yan Chan, Claire Entwisle, Giuseppe Ercoli, Elise Ramos-Sevillano, Ann McIlgorm, Paola Cecchini, Christopher Bailey, Oliver Lam, Gail Whiting, Nicola Green, David Goldblatt, Jun X. Wheeler, Jeremy S. Brown, Liise-anne Pirofski
Infection and Immunity.2022;[Epub] CrossRef
Non-capsular based immunization approaches to prevent Streptococcus pneumoniae infection
Pedro H. Silva, Yaneisi Vázquez, Camilo Campusano, Angello Retamal-Díaz, Margarita K. Lay, Christian A. Muñoz, Pablo A. González, Alexis M. Kalergis, Susan M. Bueno
Frontiers in Cellular and Infection Microbiology.2022;[Epub] CrossRef
Pneumococcal Choline-Binding Proteins Involved in Virulence as Vaccine Candidates
Julio Sempere, Mirella Llamosí, Idoia del Río Menéndez, Beatriz López Ruiz, Mirian Domenech, Fernando González-Camacho
Vaccines.2021; 9(2): 181. CrossRef
Immune Responses to Irradiated Pneumococcal Whole Cell Vaccine
Eunbyeol Ko, Soyoung Jeong, Min Yong Jwa, A Reum Kim, Ye-Eun Ha, Sun Kyung Kim, Sungho Jeong, Ki Bum Ahn, Ho Seong Seo, Cheol-Heui Yun, Seung Hyun Han
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Vaccines.2019; 7(1): 9. CrossRef
A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against LethalStreptococcus pneumoniaeChallenge
Win-Yan Chan, Claire Entwisle, Giuseppe Ercoli, Elise Ramos-Sevillano, Ann McIlgorm, Paola Cecchini, Christopher Bailey, Oliver Lam, Gail Whiting, Nicola Green, David Goldblatt, Jun X. Wheeler, Jeremy S. Brown, Liise-anne Pirofski
Infection and Immunity.2019;[Epub] CrossRef
Efficacy of whole-cell pneumococcal vaccine in mice: A systematic review and meta-analysis
Mona Mohammadzadeh, Babak Pourakbari, Shima Mahmoudi, Abbas Keshtkar, Mahdi Habibi-Anbouhi, Setareh Mamishi
Microbial Pathogenesis.2018; 122: 122. CrossRef
Construction and evaluation of a whole-cell pneumococcal vaccine candidate
M. Mohammadzadeh, B. Pourakbari, A. Doosti, S. Mahmoudi, M. Habibi-Anbouhi, S. Mamishi
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Gamma-irradiation of Streptococcus pneumoniae for the use as an immunogenic whole cell vaccine
Min Yong Jwa, Soyoung Jeong, Eun Byeol Ko, A Reum Kim, Hyun Young Kim, Sun Kyung Kim, Ho Seong Seo, Cheol-Heui Yun, Seung Hyun Han
Journal of Microbiology.2018; 56(8): 579. CrossRef
spd1672, a novel in vivo-induced gene, affects inflammatory response in a murine model of Streptococcus pneumoniae infection
Lingling Gan, Xuemei Zhang, Xiuyu Xu, Wenchun Xu, Chang Lu, Jin Cui, Hong Wang
Canadian Journal of Microbiology.2018; 64(6): 401. CrossRef
Heterologous prime-boost immunization with live SPY1 and DnaJ protein of Streptococcus pneumoniae induces strong Th1 and Th17 cellular immune responses in mice
Yulan Qiu, Xuemei Zhang, Hong Wang, Xinyuan Zhang, Yunjun Mo, Xiaoyu Sun, Jichao Wang, Yibing Yin, Wenchun Xu
Journal of Microbiology.2017; 55(10): 823. CrossRef
Panel 6: Vaccines
Melinda M. Pettigrew, Mark R. Alderson, Lauren O. Bakaletz, Stephen J. Barenkamp, Anders P. Hakansson, Kevin M. Mason, Johanna Nokso‐Koivisto, Janak Patel, Stephen I. Pelton, Timothy F. Murphy
Otolaryngology–Head and Neck Surgery.2017;[Epub] CrossRef
Attenuated Streptococcus pneumoniae vaccine candidate SPY1 promotes dendritic cell activation and drives a Th1/Th17 response
Song Gao, Lingbin Zeng, Xuemei Zhang, Yingying Wu, Jingjing Cui, Zhixin Song, Xiaoyu Sun, Hong Wang, Yibing Yin, Wenchun Xu
Immunology Letters.2016; 179: 47. CrossRef
SEROTYPE-INDEPENDENT VACCINES AGAINST PNEUMOCOCCAL INFECTION
I. B. Semenova, N. A. Mikhailova
Journal of microbiology, epidemiology and immunobiology.2016; 93(4): 76. CrossRef
Compound 48/80 acts as a potent mucosal adjuvant for vaccination against Streptococcus pneumoniae infection in young mice
Lingbin Zeng, Yusi Liu, Hong Wang, Pu Liao, Zhixin Song, Song Gao, Yingying Wu, Xuemei Zhang, Yibing Yin, Wenchun Xu
Vaccine.2015; 33(8): 1008. CrossRef
Mucosal Immunization with the Live Attenuated Vaccine SPY1 Induces Humoral and Th2-Th17-Regulatory T Cell Cellular Immunity and Protects against Pneumococcal Infection
Xiuyu Xu, Hong Wang, Yusi Liu, Yiping Wang, Lingbing Zeng, Kaifeng Wu, Jianmin Wang, Feng Ma, Wenchun Xu, Yibing Yin, Xuemei Zhang, A. Camilli
Infection and Immunity.2015; 83(1): 90. CrossRef

Adjuvant Efficacy of mOMV against Avian Influenza Virus Infection in Mice: Byeong-Jae Lee , Sang-Ho Lee , Min-Suk Song , Philippe Noriel Q. Pascua , Hyeok-il Kwon , Su-Jin Park , Eun-Ha Kim , Arun Decano , Se Mi Kim , Gyo Jin Lim , Doo-Jin Kim , Kyu-Tae Chang , Sang-Hyun Kim , Young Ki Choi; J. Microbiol. 2013;51(5):682-688. Published online October 31, 2013; DOI: https://doi.org/10.1007/s12275-013-3411-3

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Abstract PDF: Highly pathogenic avian influenza H5N1 viruses are found chiefly in birds and have caused severe disease and death in infected humans. Development of influenza vaccines capable of inducing heterosubtypic immunity against a broad range of influenza viruses is the best option for the preparedness, since vaccination remains the principal method in controlling influenza viral infections. Here, a mOMV-adjuvanted recombinant H5N2 (rH5N2) whole virus antigen vaccine with A/Environment/Korea/W149/06(H5N1)-derived H5 HA and A/Chicken/Korea/ma116/04(H9N2)-derived N2 NA in the backbone of A/Puerto Rico/8/34(H1N1) was prepared and generated by reverse genetics. Groups of mice were vaccinated by a prime-boost regime with the rH5N2 vaccine (1.75 μg of HA with/without 10 μg mOMV or aluminum hydroxide adjuvant for comparison). At two weeks post-immunizations, vaccinated mice were challenged with lethal doses of 103.5 EID50/ml of H5N1 or H9N2 avian influenza viruses, and were monitored for 15 days. Both mOMV- and alum-adjuvant vaccine groups had high survival rates after H5N1 infection and low levels of body weight changes compared to control groups. Interestingly, the mOMV-adjuvanted group induced better cross-reactive antibody responses serologically and promoted cross-protectivity against H5N1 and H9N2 virus challenges. Our results suggest that mOMV could be used as a vaccine adjuvant in the development of effective vaccines used to control influenza A virus transmission.

Review

MINIREVIEW] Development of Diagnostic and Vaccine Markers Through Cloning, Expression, and Regulation of Putative Virulence-Protein-Encoding Genes of Aeromonas hydrophila: Vijai Singh , Dharmendra Kumar Chaudhary , Indra Mani , Rohan Jain , B.N. Mishra; J. Microbiol. 2013;51(3):275-282. Published online June 28, 2013; DOI: https://doi.org/10.1007/s12275-013-2437-x

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Abstract PDF

Aeromonas hydrophila is an opportunistic bacterial pathogen that is associated with a number of diseases in fish, amphibians, reptiles, and humans. In fish it causes several disease symptoms including tail and skin rot, and haemorrhagic septicemia; in human it causes soft-tissue wound infection and diarrhoea. The pathogenesis of A. hydrophila is multifactorial, but the mechanism is unknown so far. It is considered to be mediated by expression and secretion of extracellular proteins such as aerolysin, lipase, chitinase, amylase, gelatinase, hemolysins, and enterotoxins. A number of the putative virulence-protein-encoding genes that are present in the genome of A. hydrophila have been targeted by PCR for molecular diagnosis. These significant genes are also targeted for over-production of proteins by cloning and expression methods. In this review, we emphasize recent progress in the cloning, expression, and regulation of putative virulence-protein-encoding genes of A. hydrophila for a better understanding of the pathogenesis and also help to provide effective strategies for control of diseases.

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Research Support, Non-U.S. Gov'ts

Identification of Conserved Surface Proteins as Novel Antigenic Vaccine Candidates of Actinobacillus pleuropneumoniae: Xiabing Chen , Zhuofei Xu , Lu Li , Huanchun Chen , Rui Zhou; J. Microbiol. 2012;50(6):978-986. Published online December 30, 2012; DOI: https://doi.org/10.1007/s12275-012-2214-2

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Actinobacillus pleuropneumoniae is an important swine respiratory pathogen causing great economic losses worldwide. Identification of conserved surface antigenic proteins is helpful for developing effective vaccines. In this study, a genome-wide strategy combined with bioinformatic and experimental approaches, was applied to discover and characterize surface-associated immunogenic proteins of A. pleuropneumoniae. Thirty nine genes encoding outer membrane proteins (OMPs) and lipoproteins were identified by comparative genomics and gene expression profiling as beinghighly conserved and stably transcribed in the different serotypes of A. pleuropneumoniae reference strains. Twelve of these conserved proteins were successfully expressed in Escherichia coli and their immunogenicity was estimated by homologous challenge in the mouse model, and then three of these proteins (APJL_0126, HbpA and OmpW) were further tested in the natural host (swine) by homologous and heterologous challenges. The results showed that these proteins could induce high titers of antibodies, but vaccination with each protein individually elicited low protective immunity against A. pleuropneumoniae. This study gives novel insights into immunogenicity of the conserved OMPs and lipoproteins of A. pleuropneumoniae. Although none of the surface proteins characterized in this study could individually induce effective protective immunity against A. pleuropneumoniae, they are potential candidates for subunit vaccines in combination with Apx toxins.

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Identification of candidate vaccine antigens using 2-D gel electrophoresis and immunoproteomics for cross protection against Glaesserella parasuis
Samantha J. Hau, Kirsten C. Eberle, Jarlath E. Nally, Daniel W. Nielsen, John D. Lippolis, Susan L. Brockmeier
Veterinary Microbiology.2025; 307: 110594. CrossRef
Review of advanced research on swine Actinobacillus pleuropneumoniae vaccine development strategy
Adehanom Baraki Tesfaye, Rui Han, Zhengyu Tao, Liuchao You, Jiayao Zhu, Pengcheng Gao, Lei Fu, Yuefeng Chu
Frontiers in Immunology.2025;[Epub] CrossRef
De novo identification of bacterial antigens of a clinical isolate by combining use of proteosurfaceomics, secretomics, and BacScan technologies
Jinyue Yang, Xueting Zhang, Junhua Dong, Qian Zhang, Erchao Sun, Cen Chen, Zhuangxia Miao, Yifei Zheng, Nan Zhang, Pan Tao
Frontiers in Immunology.2023;[Epub] CrossRef
Identification of a Novel Linear B-Cell Epitope of HbpA Protein from Glaesserella parasuis Using Monoclonal Antibody
Geyan Liu, Kang Wang, Zhen Yang, Xiaoyu Tang, Yung-Fu Chang, Ke Dai, Xinwei Tang, Bangdi Hu, Yiwen Zhang, Sanjie Cao, Xiaobo Huang, Qigui Yan, Rui Wu, Qin Zhao, Senyan Du, Xintian Wen, Yiping Wen
International Journal of Molecular Sciences.2023; 24(10): 8638. CrossRef
Proteomic and immunoproteomic insights into the exoproteome of Actinobacillus pleuropneumoniae, the causative agent of porcine pleuropneumonia
Stelli G. Stancheva, Janna Frömbling, Elena L. Sassu, Isabel Hennig-Pauka, Andrea Ladinig, Wilhelm Gerner, Tom Grunert, Monika Ehling-Schulz
Microbial Pathogenesis.2022; 172: 105759. CrossRef
Genome-wide screening of lipoproteins in Actinobacillus pleuropneumoniae identifies three antigens that confer protection against virulent challenge
Yurou Cao, Lulu Gao, Li Zhang, Lixiang Zhou, Jihong Yang, Lingfu Deng, Jin Zhao, Chao Qi, Jinlin Liu
Scientific Reports.2020;[Epub] CrossRef
The roles of flp1 and tadD in Actinobacillus pleuropneumoniae pilus biosynthesis and pathogenicity
Tingting Li, Qiuhong Zhang, Rong Wang, Sihua Zhang, Jie Pei, Yaokun Li, Lu Li, Rui Zhou
Microbial Pathogenesis.2019; 126: 310. CrossRef
Recombinant ApxIV protein enhances protective efficacy againstActinobacillus pleuropneumoniaein mice and pigs
H.-C. Wu, P.-H. Yeh, K.-J. Hsueh, W.-J. Yang, C.-Y. Chu
Journal of Applied Microbiology.2018; 124(6): 1366. CrossRef
New trends in innovative vaccine development against Actinobacillus pleuropneumoniae
Abraham Loera-Muro, Carlos Angulo
Veterinary Microbiology.2018; 217: 66. CrossRef
A trivalent Apx-fusion protein delivered by E. coli outer membrane vesicles induce protection against Actinobacillus pleuropneumoniae of serotype 1 and 7 challenge in a murine model
Kui Xu, Qin Zhao, Xintian Wen, Rui Wu, Yiping Wen, Xiaobo Huang, Yong Huang, Qigui Yan, Xinfeng Han, Xiaoping Ma, Yung-Fu Chang, Sanjie Cao, Utpal Pal
PLOS ONE.2018; 13(1): e0191286. CrossRef
Identification and characterization of a novel stress-responsive outer membrane protein Lip40 from Actinobacillus pleuropneumoniae
Xuehe Hu, Hao Yan, Ke Liu, Jiansheng Hu, Chao Qi, Jihong Yang, Yanli Liu, Jin Zhao, Jinlin Liu
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Comparative proteomic analysis of the membrane proteins of two Haemophilus parasuis strains to identify proteins that may help in habitat adaptation and pathogenesis
Luhua Zhang, Yiping Wen, Ying Li, Xingliang Wei, Xuefeng Yan, Xintian Wen, Rui Wu, Xiaobo Huang, Yong Huang, Qigui Yan, Mafeng Liu, Sanjie Cao
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The Production and Immunogenicity of Human Papillomavirus Type 58 Virus-like Particles Produced in Saccharomyces cerevisiae: Hye-Lim Kwag , Hyoung Jin Kim , Don Yong Chang , Hong-Jin Kim; J. Microbiol. 2012;50(5):813-820. Published online November 4, 2012; DOI: https://doi.org/10.1007/s12275-012-2292-1

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Human papillomavirus (HPV) is the cause of most cases of cervical cancer. HPV type 58 (HPV58) is the second most frequent cause of cervical cancer and high-grade squamous intraepithelial lesions (HSIL) in Asia and South / Central America, respectively. However, there is no vaccine against HPV58, although there are commercially available vaccines against HPV16 and 18. In this study, we produced HPV58 L1 protein from Saccharomyces cerevisiae, and investigated its immunogenicity. We first determined the optimum period of culture for obtaining HPV58 L1. We found that a considerable portion of the HPV58 L1 resulting from 48 h culture cannot be recovered by purification, while the HPV58 L1 resulting from 144 h culture is recovered efficiently: the yield of HPV58 L1 finally recovered from 144 h culture was 2.3 times higher than that from 48 h culture, although the production level of L1 protein from 144 h culture was lower than that from 48 h culture. These results indicate that the proportion of functional L1 protein from 144 h-cultured cells is significantly higher than that of 48 h-cultured cells. The HPV58 L1 purified from the 144 h culture was correctly assembled into structures similar to naturally occurring HPV virions. Immunization with the HPV58 L1 efficiently elicited anti-HPV58 neutralizing antibodies and antigen-specific CD4+ and CD8+ T cell proliferations, without the need for adjuvant. Our findings provide a convenient method for obtaining substantial amounts of highly immunogenic HPV58 L1 from S. cerevisiae.

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Xiaowen Wang, Xiangqian Xiao, Miao Zhao, Wei Liu, Lin Pang, Xin Sun, Shan Cen, Burton B. Yang, Yuming Huang, Wang Sheng, Yi Zeng
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Virus-like particles for enterovirus 71 produced from Saccharomyces cerevisiae potently elicits protective immune responses in mice
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Immune Response Induced by ppGpp-Defective Salmonella enterica serovar Gallinarum in Chickens: Sang-Ik Park , Jae-Ho Jeong , Hyon E. Choy , Joon Haeng Rhee , Hee-Sam Na , Tae-Hoon Lee , Moon Her , Kyoung-Oh Cho , Yeongjin Hong; J. Microbiol. 2010;48(5):674-681. Published online November 3, 2010; DOI: https://doi.org/10.1007/s12275-010-0179-6

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To protect chickens from typhoid caused by Salmonella enterica serovar Gallinarum (S. Gallinarum), the attenuated 9R strain has been used in the field as a vaccine. However, safety concerns have been raised because the mutations in 9R are undefined while its efficacy is still a question under debate. A global regulator, ppGpp, synthesized by RelA and SpoT, has been shown to induce various virulence genes in S. Gallinarum (Jeong et al., 2008). In this study, two mutant strains defective in ppGpp-synthesis were constructed in wild-type S. Gallinarum (∆ppGpp) and 9R strain (9R-∆ppGpp) backgrounds and tested as live vaccines in chickens. After oral inoculation, the LD50 values of ∆ppGpp and 9R-∆ppGpp were approximately 5×1010 colony forming unit (CFU) similarly as 9R strain, which was ~105-fold higher than that of the wildtype S. Gallinarum strain. Immunological analyses revealed immunization with either of the two attenuated ppGpp-defective strains induced significant antibody responses, the production of antibody-secreting B cells in blood, proliferation of CD4+ and CD8+ T cells in the spleen, and splenic expression of proinflammatory cytokines, such as IFN-γ and TGF-β4, at levels comparable to the 9R strain. Chickens immunized with the mutants (1×108 CFU) were 80% protected against oral challenge with 1×109 wild-type virulent bacteria (4,000-fold LD50 dose), similar to the level of protection achieved by 9R immunization. Based on these data, live attenuated ∆ppGpp-defective strains may serve as novel vaccines to control fowl typhoid in chickens.

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Mutating both relA and spoT of enteropathogenic Escherichia coli E2348/69 attenuates its virulence and induces interleukin 6 in vivo
Jun Bong Lee, Se Kye Kim, Dalmuri Han, Jang Won Yoon
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Vaccines to Control Salmonella in Poultry
Roy Curtiss
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Evaluation of Safety and Protective Efficacy of a waaJ and spiC Double Deletion Korean Epidemic Strain of Salmonella enterica Serovar Gallinarum
Jun-Feng Zhang, Ke Shang, Bai Wei, Yea-Jin Lee, Jong-Yeol Park, Hyung-Kwan Jang, Se-Yeoun Cha, Min Kang
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Survival of the Fittest: The Relationship of (p)ppGpp With Bacterial Virulence
Shivani Kundra, Cristina Colomer-Winter, José A. Lemos
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О. М. Sen, О. О. Saliy, V. I. Mazurkevych, Y. A. Sobko
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Zhili Li, Yuejia Cai, Guozhi Liang, Saeed El-Ashram, Minmin Mei, Wenjing Huang, Xiaowen Li, Wenfeng Li, Cheng He, Shujian Huang
Scientific Reports.2018;[Epub] CrossRef
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Gayeon Won, Atul A. Chaudhari, John Hwa Lee
Clinical and Experimental Vaccine Research.2016; 5(2): 148. CrossRef
Characterization of the RelBbu Regulon in Borrelia burgdorferi Reveals Modulation of Glycerol Metabolism by (p)ppGpp
Julia V. Bugrysheva, Christopher J. Pappas, Darya A. Terekhova, Radha Iyer, Henry P. Godfrey, Ira Schwartz, Felipe C. Cabello, Petros C. Karakousis
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Chetan V. Jawale, Atul A. Chaudhari, John Hwa Lee
Vaccine.2014; 32(9): 1093. CrossRef
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Chetan V. Jawale, John Hwa Lee
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Nak-Hyung Lee, Jung-Ah Lee, Seung-Yong Park, Chang-Seon Song, In-Soo Choi, Joong-Bok Lee
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Construction of a Salmonella Gallinarum ghost as a novel inactivated vaccine candidate and its protective efficacy against fowl typhoid in chickens
Atul A Chaudhari, Chetan V Jawale, Sam Woong Kim, John Hwa Lee
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Immunological Responses Induced by asd and wzy/asd Mutant Strains of Salmonella enterica serovar Typhimurium in BALB/c Mice: Hong Hua Piao , Vo Thi Minh Tam , Hee Sam Na , Hyun Ju Kim , Phil Youl Ryu , Soo Young Kim , Joon Haeng Rhee , Hyon E. Choy , Suhng Wook Kim , Yeongjin Hong; J. Microbiol. 2010;48(4):486-495. Published online August 20, 2010; DOI: https://doi.org/10.1007/s12275-010-0023-z

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Attenuated bacteria have long been developed as vaccine candidates but can have some disadvantages, such as the potential for damage to immune organs due to insufficient clearance. To minimize these disadvantages, we generated Salmonella enterica serovar Typhimurium mutants SHJ2104 (asd::cm) and HTSaYA (wzy::km, asd::cm). The wzy gene codes for the O-antigen polymerase, which is involved in lipopolysaccharide (LPS) biosynthesis, and asd codes for aspartate ß- semialdehyde dehydrogenase, which participates in cell wall formation. The strains synthesized LPS with a short-chain length, and showed lower cytotoxicity and reduced intracellular proliferation in animal cells compared to wild-type bacteria. After oral infection, the mutants were cleared in immune tissues, including the Peyer’s patch, mesenteric lymph node, and spleen, within 5 days. The LD50 of the mutants in Balb/c mice was estimated to be 106 higher than wild-type bacteria when administered either via an oral or i.p. route, indicating that the two strains are highly attenuated. To compare the immune response to and protective effects of the mutants against wild-type bacterial infection, we inoculated the mutants into mice via an oral (1×1010 CFU) or i.p. (1×107 CFU) route once or twice at a two week interval. All immune responses, such as serum IgG and secretory IgA levels, cytokine production, and delayed hypersensitivity, were highly induced by two rounds of immunization. HTSaYA and SHJ2104 induced similar immune responses, and mice immunized with HTSaYA or SHJ2104 via an i.p. route were protected against wild-type Salmonella infection even at 100-fold of the LD50 (5×106 CFU). Taken together, these data indicate that HTSaYA and SHJ2104 could be developed as live attenuated Salmonella vaccine candidates.

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The Evolution of Vaccines Development across Salmonella Serovars among Animal Hosts: A Systematic Review
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Korean Journal of Veterinary Research.2015; 55(1): 1. CrossRef
Live attenuated vaccines for invasive Salmonella infections
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Attenuating gene expression (AGE) for vaccine development
David W Pascual, Zhiyong Suo, Ling Cao, Recep Avci, Xinghong Yang
Virulence.2013; 4(5): 384. CrossRef
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Kiju Kim, Dooree Kim, Jisun Sun, Soyeon Park, Youngjae Cho, Hyun-Jeong Ko, Hong-Gu Joo, Tae-Wook Hahn
Korean Journal of Veterinary Research.2013; 53(2): 95. CrossRef
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Protection Against Helicobacter pylori Infection by a Trivalent Fusion Vaccine Based on a Fragment of Urease B-UreB414: Li Wang Wang , Xiao-Fei Liu , Shi Yun , Xiao-Peng Yuan , Xu-Hu Mao , Chao Wu , Wei-Jun Zhang , Kai-Yun Liu , Gang Guo , Dong-Shui Lu , Wen-De Tong , Ai-Dong Wen , Quan-Ming Zou; J. Microbiol. 2010;48(2):223-228. Published online May 1, 2010; DOI: https://doi.org/10.1007/s12275-009-0233-4

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A multivalent fusion vaccine is a promising option for protection against Helicobacter pylori infection. In this study, UreB414 was identified as an antigenic fragment of urease B subunit (UreB) and it induced an antibody inhibiting urease activity. Immunization with UreB414 partially protected mice from H. pylori infection. Furthermore, a trivalent fusion vaccine was constructed by genetically linking heat shock protein A (HspA), H. pylori adhesin A (HpaA), and UreB414, resulting in recombinant HspA-HpaA-UreB414 (rHHU). Its protective effect against H. pylori infection was tested in BALB/c mice. Oral administration of rHHU significantly protected mice from H. pylori infection, which was associated with H. pylori-specific antibody production and Th1/Th2-type immune responses. The results show that a trivalent fusion vaccine efficiently combats H. pylori infection, and that an antigenic fragment of the protein can be used instead of the whole protein to construct a multivalent vaccine.

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Junhong Wang, Shan Gao, Tao Zhang, Lin Kang, Wuchun Cao, Na Xu, Wensen Liu, Jinglin Wang
Human Vaccines & Immunotherapeutics.2014; 10(4): 938. CrossRef
Protection against pneumococcal infection elicited by immunization with multiple pneumococcal heat shock proteins
Ju Cao, Xiaojiao Zhang, Yi Gong, Yuhong Zhang, Yali Cui, Xiaofei Lai, Yibing Yin, Meijuan Li, Dairong Li, Liping Zhang
Vaccine.2013; 31(35): 3564. CrossRef
Inflammation, Immunity, and Vaccine Development for Helicobacter pylori
Anne Müller, Jay V. Solnick
Helicobacter.2011; 16(s1): 26. CrossRef
Mimotopes selected with a neutralizing antibody against urease B from Helicobacter pyloriinduce enzyme inhibitory antibodies in mice upon vaccination
Yan Li, Yunshan Ning, Yundan Wang, Dandan Peng, Yaodong Jiang, Lili Zhang, Min Long, Jun Luo, Ming Li
BMC Biotechnology.2010;[Epub] CrossRef

Fusion Expression and Immunogenicity of EHEC EspA-Stx2A1 Protein: Implications for the Vaccine Development: Yan Cheng , Youjun Feng , Ping Luo , Jiang Gu , Shu Yu , Wei-jun Zhang , Yan-qing Liu , Qing-xu Wang , Quan-ming Zou , Xu-hu Mao; J. Microbiol. 2009;47(4):498-505. Published online September 9, 2009; DOI: https://doi.org/10.1007/s12275-009-0116-8

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Abstract PDF

Shiga toxin 2 (Stx2) is a major virulence factor for enterohemorrhagic Escherichia coli (EHEC), which is encoded by λ lysogenic phage integrated into EHEC chromosome. Stx2A1, A1 subunit of Stx2 toxin has gathered extensive concerns due to its potential of being developed into a vaccine candidate. However, the substantial progress is hampered in part for the lack of a suitable in vitro expression system. Here we report use of the prokaryotic system pET-28a::espA-Stx2A1/BL21 to carry out the fusion expression of Stx2A1 which is linked to E. coli secreted protein A (EspA) at its N-terminus. Under the IPTG induction, EspA- Stx2A1 fusion protein in the form of inclusion body was obtained successfully, whose expression level can reach about 40% of total bacterial protein at 25°C, much higher than that at 37°C. Western blot test suggested the refolded fusion protein is of excellent immuno-reactivity with both monoclonal antibodies, which are specific to EspA and Stx2A1, respectively. Anti-sera from Balb/c mice immunized with the EspA-Stx2A1 fusion protein were found to exhibit strong neutralization activity and protection capability in vitro and in vivo. These data have provided a novel feasible method to produce Stx2A1 in large scale in vitro, which is implicated for the development of multivalent subunit vaccines candidate against EHEC O157:H7 infections.

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Miguel O’Ryan, Roberto Vidal, Felipe del Canto, Juan Carlos Salazar, David Montero
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Anti-Tumor Activity of Acinetobacter baumannii Outer Membrane Protein A on Dendritic Cell-Based Immunotherapy against Murine Melanoma: Jun Sik Lee , Jung Wook Kim , Chul Hee Choi , Won Kee Lee , Hae Young Chung , Je Chul Lee; J. Microbiol. 2008;46(2):221-227. Published online June 11, 2008; DOI: https://doi.org/10.1007/s12275-008-0052-z

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Abstract PDF

Acinetobacter baumannii outer membrane protein A (AbOmpA) is a major surface protein that is an important pathogen-associated molecular pattern. Based on our previous findings that AbOmpA induced the phenotypic maturation of dendritic cells (DCs) and drove the Th1 immune response in vitro, we investigated the therapeutic efficacy of AbOmpA-pulsed DC vaccines in a murine melanoma model. The surface expression of co-stimulatory molecules (CD80 and CD86) and major histocompatibility complex class I and II molecules was higher in DCs pulsed with AbOmpA alone or with a combination of B16F10 cell lysates than that of DCs pulsed with B16F10 cell lysates. AbOmpA stimulated the maturation of murine splenic DCs in vivo. In a therapeutic model of murine melanoma, AbOmpA-pulsed DCs significantly retarded tumor growth and improved the survival of tumor-bearing mice. AbOmpA-pulsed DCs significantly enhanced CD8+, interleukin-2+ T cells and CD4+, interferon-γ+ T cells in tumor-bearing mice. These results provide evidence that AbOmpA may be therapeutically useful in adjuvant DC immunotherapy against poorly immunogenic melanoma without tumor-specific antigens.

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AbOmpA in Acinetobacter baumannii: exploring virulence mechanisms of outer membrane-integrated and outer membrane vesicle-associated AbOmpA and developing anti-infective agents targeting AbOmpA
Man Hwan Oh, Md Minarul Islam, Nayeong Kim, Chul Hee Choi, Minsang Shin, Woo Shik Shin, Je Chul Lee
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Journal Articles

Outer Membrane Protein H for Protective Immunity Against Pasteurella multocida: Jeongmin Lee , Young Bong Kim , Moosik Kwon; J. Microbiol. 2007;45(2):179-184.; DOI: https://doi.org/2514 [pii]

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Abstract PDF: Pasteurella multocida, a Gram-negative facultative anaerobic bacterium, is a causative animal pathogen in porcine atrophic rhinitis and avian fowl cholera. For the development of recombinant subunit vaccine against P. multocida, we cloned and analyzed the gene for outer membrane protein H (ompH) from a native strain of Pasteurella multocida in Korea. The OmpH had significant similarity in both primary and secondary structure with those of other serotypes. The full-length, and three short fragments of ompH were expressed in E. coli and the recombinant OmpH proteins were purified, respectively. The recombinant OmpH proteins were antigenic and detectable with antisera produced by either immunization of commercial vaccine for respiratory disease or formalin-killed cell. Antibodies raised against the full-length OmpH provided strong protection against P. multocida, however, three short fragments of recombinant OmpHs, respectively, showed slightly lower protection in mice challenge. The recombinant OmpH might be a useful vaccine candidate antigen for P. multocida.

Analysis of Immune Responses Against Nucleocapsid Protein of the Hantaan Virus Elicited by Virus Infection or DNA Vaccination: Gyu-Jin Woo , Eun-Young Chun , Keun Hee Kim , Wankee Kim; J. Microbiol. 2005;43(6):537-545.; DOI: https://doi.org/2292 [pii]

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Abstract PDF: Even though neutralizing antibodies against the Hantaan virus (HTNV) has been proven to be critical against viral infections, the cellular immune responses to HTNV are also assumed to be important for viral clearance. In this report, we have examined the cellular and humoral immune responses against the HTNV nucleocapsid protein (NP) elicited by virus infection or DNA vaccination. To examine the cellular immune response against HTNV NP, we used H-2Kb restricted T-cell epitopes of NP. The NP-specific CD8+ T cell response was analyzed using a 51Cr-release assay, intracellular cytokine staining assay, enzyme-linked immunospot assay and tetramer binding assay in C57BL/6 mice infected with HTNV. Using these methods, we found that HTNV infection elicited a strong NP-specific CD8+ T cell response at eight days after infection. We also found that several different methods to check the NP-specific CD8+ T cell response showed a very high correlation among analysis. In the case of DNA vaccination by plasmid encoding nucleocapsid gene, the NP-specific antibody response was elicited 2 ~ 4 weeks after immunization and maximized at 6~8 weeks. NP-specific CD8+ T cell response reached its peak 3 weeks after immunization. In a challenge test with the recombinant vaccinia virus expressing NP (rVV-HTNV-N), the rVV-HTNV-N titers in DNA vaccinated mice were decreased about 100-fold compared to the negative control mice.

Immunization with Major Outer Membrane Protein of Vibrio vulnificus Elicits Protective Antibodies in a Murine Model: Cho-Rok Jung , Min-Jung Park , Moon-Soo Heo; J. Microbiol. 2005;43(5):437-442.; DOI: https://doi.org/2278 [pii]

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Abstract PDF: Sera from rabbits were infected with Vibrio vulnificus containing an antibody against major outer membrane protein (MOMP). MOMP of V. vulnificus ATCC 27562 were isolated and purified by Sarkosyl and TritonX-100 dual treatment. Molecular size of MOMP was identified as 36-kDa on 13% SDS-PAGE. The sequence of the first 26 amino acid residues from the N-terminal end of the protein is AELYNQDGTSLDMGGRAEARLSMKDG , which is a perfect match with OmpU of V. vulnificus CMCP6 and YJ016. MOMP specific IgM and IgG were investigated in groups of mice. The group of mice immunized with MOMP and Alum showed higher levels of IgG2b than the group immunized with only MOMP. Vaccination with MOMP resulted in protective antibodies in the mouse infection experiment.

Reviews

Shigellosis: Swapan Kumar Niyogi; J. Microbiol. 2005;43(2):133-143.; DOI: https://doi.org/2172 [pii]

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Abstract PDF: Shigellosis is a global human health problem. Four species of Shigella i.e. S. dysenteriae, S. flexneri, S. boydii and S. sonnei are able to cause the disease. These species are subdivided into serotypes on the basis of O-specific polysaccharide of the LPS. Shigella dysenteriae type 1 produces severe disease and may be associated with life-threatening complications. The symptoms of shigellosis include diarrhoea and/or dysentery with frequent mucoid bloody stools, abdominal cramps and tenesmus. Shigella spp. cause dysentery by invading the colonic mucosa. Shigella bacteria multiply within colonic epithelial cells, cause cell death and spread laterally to infect and kill adjacent epithelial cells, causing mucosal ulceration, inflammation and bleeding. Transmission usually occurs via contaminated food and water or through person-to-person contact. Laboratory diagnosis is made by culturing the stool samples using selective/differential agar media. Shigella spp. are highly fragile organism and considerable care must be exercised in collecting faecal specimens, transporting them to the laboratories and in using appropriate media for isolation. Antimicrobial agents are the mainstay of therapy of all cases of shigellosis. Due to the global emergence of drug resistance, the choice of antimicrobial agents for treating shigellosis is limited. Although single dose of norfloxacin and ciprofloxacin has been shown to be effective, they are currently less effective against S. dysenteriae type 1 infection. Newer quinolones, cephalosporin derivatives, and azithromycin are the drug of choice. However, fluoroquinolone-resistant S. dysenteriae type 1 infection have been reported. Currently, no vaccines against Shigella infection exist. Both live and subunit parenteral vaccine candidates are under development. Because immunity to Shigella is serotype-specific, the priority is to develop vaccine against S. dysenteriae type 1 and S. flexneri type 2a. Shigella species are important pathogens responsible for diarrhoeal diseases and dysentery occurring all over the world. The morbidity and mortality due to shigellosis are especially high among children in developing countries. A recent review of literature (Kotloff et al.,1999) concluded that, of the estimated 165 million cases of Shigella diarrhoea that occur annually, 99% occur in developing countries, and in developing countries 69% of episodes occur in children under five years of age. Moreover, of the ca.1.1 million deaths attributed to Shigella infections in developing countries, 60% of deaths occur in the under-five age group. Travellers from developed to developing regions and soldiers serving under field conditions are also at an increased risk to develop shigellosis.

Strategies Against Human Papillomavirus Infection and Cervical Cancer: Woon-Won Jung , Taehoon Chun , Donggeun Sul , Kwang Woo Hwang , Hyung-Sik Kang , Duck Joo Lee , In-Kwon Han; J. Microbiol. 2004;42(4):255-266.; DOI: https://doi.org/2112 [pii]

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Abstract PDF: Papillomaviruses infect a wide variety of animals, including humans. The human papillomavirus (HPV), in particular, is one of the most common causes of sexually transmitted disease. More than 200 types of HPV have been identified by DNA sequence data, and 85 HPV genotypes have been well characterized to date. HPV can infect the basal epithelial cells of the skin or inner tissue linings, and are, accordingly, categorized as either cutaneous or mucosal type. HPV is associated with a panoply of clinical conditions, ranging from innocuous lesions to cervical cancer. In the early 1980s, studies first reported a link between cervical cancer and genital HPV infection. Genital HPV infections are now recognized to be a major risk factor in at least 95% of cervical cancers. 30 different HPV genotypes have been identified as causative of sexually transmitted diseases, most of which induce lesions in the cervix, vagina, vulva, penis, and anus, as the result of sexual contact. There is also direct evidence demonstrating that at least four of these genotypes are prerequisite factors in cervical cancer. The main aim of this review was to evaluate the current literature regarding the pathovirology, diagnostics, vaccines, therapy, risk groups, and further therapeutic directions for HPV infections. In addition, we reviewed the current status of HPV infections in South Korean women, as evidenced by our data.

Evaluation of the Efficacy of a Pre-pandemic H5N1 Vaccine (MG1109) in Mouse and Ferret Models: Min-Suk Song , Ho-Jin Moon , Hyeok-il Kwon , Philippe Noriel Q. Pascua , Jun Han Lee , Yun Hee Baek , Kyu-Jin Woo , Juhee Choi , Sangho Lee , Hyunseung Yoo , In gyeong Oh , Yeup Yoon , Jong-Bok Rho , Moon-Hee Sung , Seung-Pyo Hong , Chul-Joong Kim , Young Ki Choi; J. Microbiol. 2012;50(3):487-488.

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Abstract PDF: The threat of a highly pathogenic avian influenza (HPAI) H5N1 virus causing the next pandemic remains a major concern. In this study, we evaluated the immunogenicity and efficacy of an inactivated whole-virus H5N1 pre-pandemic vaccine (MG1109) formulated by Green Cross Co., Ltd containing the hemagglutinin (HA) and neuraminidase (NA) genes of the clade 1 A/Vietnam/1194/04 virus in the backbone of A/Puerto Rico/8/34 (RgVietNam/04xPR8/34). Administration of the MG1109 vaccine (2-doses) in mice and ferrets elicited high HI and SN titers in a dose-dependent manner against the homologous (RgVietNam/04xPR8/34) and various heterologous H5N1 strains, (RgKor/W149/06xPR8/34, RgCambodia/04xPR8/34, RgGuangxi/05xPR8/34), including a heterosubtypic H5N2 (A/Aquatic bird/orea/W81/05) virus. However, efficient cross-reactivity was not observed against heterosubtypic H9N2 (A/Ck/Korea/H0802/08) and H1N1 (PR/8/34) viruses. Mice immunized with 1.9 μg HA/dose of MG1109 were completely protected from lethal challenge with heterologous wild-type HPAI H5N1 A/EM/Korea/W149/06 (clade 2.2) and mouse-adapted H5N2 viruses. Furthermore, ferrets administered at least 3.8 μg HA/dose efficiently suppressed virus growth in the upper respiratory tract and lungs. Vaccinated mice and ferrets also demonstrated attenuation of clinical disease signs and limited virus spread to other organs. Thus, this vaccine provided immunogenic responses in mouse and ferret models even against challenge with heterologous HPAI H5N1 and H5N2 viruses. Since the specific strain of HPAI H5N1 virus that would potentially cause the next outbreak is unknown, pre-pandemic vaccine preparation that could provide crossprotection against various H5 strains could be a useful approach in the selection of promising candidate vaccines in the future.

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