Research article
- Establishment of a CD46 and desmoglein-2 expressing mouse model for human adenovirus type 55 vaccine evaluation
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Jung-ah Choi, Eunji Yang, Shing Young Noh, Dae-Im Jung, Yun Jeong Park, Ji Heun Jeong, Hye Yun Jeong, Manki Song, Soon-Hwan Kwon, Sang Hwan Seo
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J. Microbiol. 2026;64(9):e2605005. Published online September 18, 2026
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DOI: https://doi.org/10.71150/jm.2605005
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Supplementary Material
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Human adenovirus type 55 (HAdV-55) is an emerging respiratory pathogen associated with severe pneumonia, for which no licensed vaccines are currently available. The lack of physiologically relevant small-animal models has limited preclinical evaluation of vaccine candidates. In this study, we generated a transgenic mouse model co-expressing human CD46 and desmoglein-2 (DSG-2), key entry receptors for HAdV-55, and evaluated its utility for vaccine efficacy testing. A bicistronic expression system enabling simultaneous expression of CD46 and DSG-2 was constructed and functionally validated in vitro, demonstrating enhanced susceptibility to HAdV-55 infection. The transgenic mice exhibited dose-dependent weight loss, robust viral replication in lung tissues, and characteristic histopathological changes following intranasal challenge, recapitulating key features of human adenoviral pneumonia. Using this model, we assessed the immunogenicity and protective efficacy of an inactivated HAdV-55 (iHAdV-55) vaccine formulated with alum. Vaccination induced strong HAdV-55-specific IgG and neutralizing antibody responses, which increased over time following prime–boost immunization. Upon viral challenge, vaccinated mice showed significantly reduced weight loss and accelerated recovery compared to controls. Viral load analysis demonstrated effective control of viral replication and clearance in vaccinated animals. Collectively, these findings establish the CD46/DSG-2 transgenic mouse as a physiologically relevant and translationally valuable model for HAdV-55 infection and demonstrate that iHAdV-55 vaccination confers robust humoral immunity and protective efficacy. This platform provides a critical tool for the development and preclinical evaluation of adenovirus-targeted vaccines and therapeutics.
Research article
- Development and analytical evaluation of a microneutralization cytopathic effect assay for human adenovirus type 55-specific neutralizing antibodies
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Dae-Im Jung, Yunjeong Park, Jung-ah Choi, Soon-Hwan Kwon, Jun Young Lee, Manki Song, Sang Hwan Seo
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J. Microbiol. 2026;64(7):e2604007. Published online July 6, 2026
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DOI: https://doi.org/10.71150/jm.2604007
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Abstract
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Supplementary Material
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Reliable quantification of neutralizing antibodies (nAb) against human adenovirus type 55 (HAdV-55) is critical for the evaluation of emerging vaccine candidates. While the plaque reduction neutralization test (PRNT) is currently the reference standard, its utility for large-scale studies is limited by low throughput, labor-intensive plaque counting, and prolonged assay times. In this study, we established and analytically validated a microneutralization assay based on cytopathic effect (MN-CPE) as a scalable alternative for HAdV-55-specific nAb quantification. Comparative performance analysis revealed that both assays maintain high dilution linearity, with coefficients of determination (R2) of 0.988 for MN-CPE and 0.9926 for PRNT. Relative accuracy assessments using high-, middle-, and low-titer reference sera demonstrated acceptable responses across the dynamic range. Notably, the MN-CPE assay allowed for the definition of a negative-control acceptance range, providing a distinct statistical advantage over PRNT, where negative-control values were consistently zero. Furthermore, both assays successfully detected HAdV-55-specific nAbs in immunized cynomolgus macaques, with no cross-reactivity observed against other HAdV types such as HAdV-4. These findings indicate that the MN-CPE assay is analytically comparable to PRNT and serves as a practical, relatively high-capacity alternative for HAdV-55 neutralization testing in clinical and preclinical vaccine research.
Article
- Mouse strain-dependent neutralizing antibody responses to Zika virus vaccines
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Sang Hwan Seo, Jung-ah Choi, Eunji Yang, Hayan Park, Dae-Im Jung, Jae-Ouk Kim, Jae Seung Yang, Manki Song
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J. Microbiol. 2025;63(8):e2504005. Published online August 31, 2025
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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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Citations
Citations to this article as recorded by

- 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 - Development and Immunogenicity Assessment of a Multi-Epitope Antigen Against Zika Virus: An In Silico and In Vivo Approach
Lígia Rosa Sales Leal, Matheus Gardini Amâncio Marques de Sena, Maria da Conceição Viana Invenção, Ingrid Andrêssa de Moura, André Luiz Santos de Jesus, Georon Ferreira de Sousa, Bárbara Rafaela da Silva Barros, Cristiane Moutinho Lagos de Melo, Lindomar
Vaccines.2025; 14(1): 31. CrossRef
Review
- Middle East Respiratory Syndrome coronavirus vaccine development: updating clinical studies using platform technologies
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Jung-ah Choi , Jae-Ouk Kim
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J. Microbiol. 2022;60(3):238-246. Published online January 28, 2022
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DOI: https://doi.org/10.1007/s12275-022-1547-8
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1,038
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Abstract
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Middle East Respiratory Syndrome coronavirus (MERS-CoV),
a contagious zoonotic virus, causes severe respiratory infection
with a case fatality rate of approximately 35% in humans.
Intermittent sporadic cases in communities and healthcare
facility outbreaks have continued to occur since its first identification
in 2012. The World Health Organization has declared
MERS-CoV a priority pathogen for worldwide research
and vaccine development due to its epidemic potential and
the insufficient countermeasures available. The Coalition for
Epidemic Preparedness Innovations is supporting vaccine development
against emerging diseases, including MERS-CoV,
based on platform technologies using DNA, mRNA, viral vector,
and protein subunit vaccines. In this paper, we review the
usefulness and structure of a spike glycoprotein as a MERSCoV
vaccine candidate molecule, and provide an update on
the status of MERS-CoV vaccine development. Vaccine candidates
based on both DNA and viral vectors coding MERSCoV
spike gene have completed early phase clinical trials. A
harmonized approach is required to assess the immunogenicity
of various candidate vaccine platforms. Platform technologies
accelerated COVID-19 vaccine development and can
also be applied to developing vaccines against other emerging
viral diseases.
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Citations
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- Global research hotspots and trends in DNA vaccine research: A bibliometric and visualization study from 2014 to 2024
Juan Zhang, Haiguo Zhang, Cuicui Yao, Lihua Gu, Shasha Dong, Yamei Wu, Lele Miao
Human Vaccines & Immunotherapeutics.2025;[Epub] CrossRef - MERS-CoV RBD-mRNA Presents Better Immunogenicity and Protection than the Spike-mRNA
Qian Liu, Abhishek K. Verma, Xiaoqing Guan, Shengnan Qian, Stanley Perlman, Lanying Du
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Annals of Medicine & Surgery.2024; 86(3): 1506. CrossRef - The many facets of CD26/dipeptidyl peptidase 4 and its inhibitors in disorders of the CNS – a critical overview
Hans-Gert Bernstein, Gerburg Keilhoff, Henrik Dobrowolny, Johann Steiner
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Jinjong Myoung
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Research Support, Non-U.S. Gov't
- Sublingual Administration of Bacteria-Expressed Influenza Virus Hemagglutinin 1 (HA1) Induces Protection against Infection with 2009 Pandemic H1N1 Influenza Virus
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Byoung-Shik Shim , Jung-ah Choi , Ho-Hyun Song , Sung-Moo Park , In Su Cheon , Ji-Eun Jang , Sun Je Woo , Chung Hwan Cho , Min-Suk Song , Hyemi Kim , Kyung Joo Song , Jae Myun Lee , Suhng Wook Kim , Dae Sub Song , Young Ki Choi , Jae-Ouk Kim , Huan Huu Nguyen , Dong Wook Kim , Young Yil Bahk , Cheol-Heui Yun , Man Ki Song
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J. Microbiol. 2013;51(1):130-135. Published online March 2, 2013
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DOI: https://doi.org/10.1007/s12275-013-2399-z
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735
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Abstract
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Influenza viruses are respiratory pathogens that continue to pose a significantly high risk of morbidity and mortality of humans worldwide. Vaccination is one of the most effective strategies for minimizing damages by influenza outbreaks. In addition, rapid development and production of efficient vaccine with convenient administration is required in case of influenza pandemic. In this study, we generated recombinant influenza virus hemagglutinin protein 1 (sHA1) of 2009 pandemic influenza virus as a vaccine candidate using a wellestablished bacterial expression system and administered it into mice via sublingual (s.l.) route. We found that s.l. immunization with the recombinant sHA1 plus cholera toxin (CT) induced mucosal antibodies as well as systemic antibodies including neutralizing Abs and provided complete protection against infection with pandemic influenza virus A/CA/04/09 (H1N1) in mice. Indeed, the protection efficacy was comparable with that induced by intramuscular (i.m.) immunization route utilized as general administration route of influenza vaccine. These results suggest that s.l. vaccination with the recombinant non-glycosylated HA1 protein offers an alternative strategy to control influenza outbreaks including pandemics.
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