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Volume 60(3); March 2022
Editorial
[SPECIAL ISSUE]Two years of COVID-19 pandemic: where are we now?
Jinjong Myoung
J. Microbiol. 2022;60(3):235-237.
DOI: https://doi.org/10.1007/s12275-022-1679-x
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Reviews
Middle East Respiratory Syndrome coronavirus vaccine development: updating clinical studies using platform technologies
Jung-ah Choi , Jae-Ouk Kim
J. Microbiol. 2022;60(3):238-246.   Published online January 28, 2022
DOI: https://doi.org/10.1007/s12275-022-1547-8
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AbstractAbstract
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.
Current status and perspectives on vaccine development against dengue virus infection
Jisang Park , Ju Kim , Yong-Suk Jang
J. Microbiol. 2022;60(3):247-254.   Published online February 14, 2022
DOI: https://doi.org/10.1007/s12275-022-1625-y
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AbstractAbstract
Dengue virus (DENV) consists of four serotypes in the family Flaviviridae and is a causative agent of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. DENV is transmitted by mosquitoes, Aedes aegypti and A. albopictus, and is mainly observed in areas where vector mosquitoes live. The number of dengue cases reported by the World Health Organization increased more than 8-fold over the last two decades from 505,430 in 2000 to over 2.4 million in 2010 to 5.2 million in 2019. Although vaccine is the most effective
method
against DENV, only one commercialized vaccine exists, and it cannot be administered to children under 9 years of age. Currently, many researchers are working to resolve the various problems hindering the development of effective dengue vaccines; understanding of the viral antigen configuration would provide insight into the development of effective vaccines against DENV infection. In this review, the current status and perspectives on effective vaccine development for DENV are examined. In addition, a plausible direction for effective vaccine development against DENV is suggested.
Transmissibility and pathogenicity of SARS-CoV-2 variants in animal models
Young-Il Kim , Mark Anthony B. Casel , Young Ki Choi
J. Microbiol. 2022;60(3):255-267.   Published online March 2, 2022
DOI: https://doi.org/10.1007/s12275-022-2033-z
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AbstractAbstract
As of February 2022, SARS-CoV-2 is still one of the most serious public health threats due to its high mortality rate and rapid spread of novel variants. Since the first outbreak in 2019, general understanding of SARS-CoV-2 has been improved through basic and clinical studies; however, knowledge gaps still exist in our understanding of the emerging novel SARSCoV- 2 variants, which impacts the corresponding development of vaccines and therapeutics. Especially, accumulation of mutations in SARS-CoV-2 and rapid spread in populations with previous immunity has resulted in selection of variants that evade the host immune response. This phenomenon threatens to render current SARS-CoV-2 vaccines ineffective for controlling the pandemic. Proper animal models are essential for detailed investigations into the viral etiology, transmission and pathogenesis mechanisms, as well as evaluation of the efficacy of vaccine candidates against recent SARS-CoV-2 variants. Further, the choice of animal model for each research topic is important for researchers to gain better knowledge of recent SARS-CoV-2 variants. Here, we review the advantages and limitations of each animal model, including mice, hamsters, ferrets, and non-human primates, to elucidate variant SARS-CoV-2 etiology and transmission and to evaluate therapeutic and vaccine efficacy.
Protective and pathogenic role of humoral responses in COVID-19
Uni Park , Nam-Hyuk Cho
J. Microbiol. 2022;60(3):268-275.   Published online March 2, 2022
DOI: https://doi.org/10.1007/s12275-022-2037-8
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AbstractAbstract
Since the advent of SARS-CoV-2 in Dec. 2019, the global endeavor to identify the pathogenic mechanism of COVID-19 has been ongoing. Although humoral immunity including neutralizing activity play an important role in protection from the viral pathogen, dysregulated antibody responses may be associated with the pathogenic progression of COVID-19, especially in high-risk individuals. In addition, SARS-CoV-2 spike-specific antibodies acquired by prior infection or vaccination act as immune pressure, driving continuous population turnover by selecting for antibody-escaping mutations. Here, we review accumulating knowledge on the potential role of humoral immune responses in COVID-19, primarily focusing on their beneficial and pathogenic properties. Understanding the multifaceted regulatory mechanisms of humoral responses during SARS-CoV-2 infection can help us to develop more effective therapeutics, as well as protective measures against the ongoing pandemic.
T cell responses to SARS-CoV-2 in humans and animals
Sameer-ul-Salam Mattoo , Jinjong Myoung
J. Microbiol. 2022;60(3):276-289.   Published online February 14, 2022
DOI: https://doi.org/10.1007/s12275-022-1624-z
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AbstractAbstract
SARS-CoV-2, the causative agent of COVID-19, first emerged in 2019. Antibody responses against SARS-CoV-2 have been given a lot of attention. However, the armamentarium of humoral and T cells may have differing roles in different viral infections. Though the exact role of T cells in COVID-19 remains to be elucidated, prior experience with human coronavirus has revealed an essential role of T cells in the outcomes of viral infections. Moreover, an increasing body of evidence suggests that T cells might be effective against SARS-CoV-2. This review summarizes the role of T cells in mouse CoV, human pathogenic respiratory CoV in general and SARSCoV- 2 in specific.
SARS-CoV-2-mediated evasion strategies for antiviral interferon pathways
Soo-Jin Oh , Ok Sarah Shin
J. Microbiol. 2022;60(3):290-299.   Published online February 5, 2022
DOI: https://doi.org/10.1007/s12275-022-1525-1
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AbstractAbstract
With global expansion of the COVID-19 pandemic and the emergence of new variants, extensive efforts have been made to develop highly effective antiviral drugs and vaccines against SARS-CoV-2. The interactions of coronaviruses with host antiviral interferon pathways ultimately determine successful viral replication and SARS-CoV-2-induced pathogenesis. Innate immune receptors play an essential role in host defense against SARS-CoV-2 via the induction of IFN production and signaling. Here, we summarize the recent advances in innate immune sensing mechanisms of SARS-CoV-2 and various strategies by which SARS-CoV-2 antagonizes antiviral innate immune signaling pathways, with a particular focus on mechanisms utilized by multiple SARS-CoV-2 proteins to evade interferon induction and signaling in host cell. Understanding the underlying immune evasion mechanisms of SARS-CoV-2 is essential for the improvement of vaccines and therapeutic strategies.
Coordinated regulation of interferon and inflammasome signaling pathways by SARS-CoV-2 proteins
Na-Eun Kim , Yoon-Jae Song
J. Microbiol. 2022;60(3):300-307.   Published online January 28, 2022
DOI: https://doi.org/10.1007/s12275-022-1502-8
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AbstractAbstract
Type I and III interferons (IFNs) and the nucleotide-binding domain (NBD) leucine-rich repeat (LRR)-containing receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome play pivotal roles in the pathogenesis of SARS-CoV-2. While optimal IFN and inflammasome responses are essential for limiting SARS-CoV-2 infection, aberrant activation of these innate immune responses is associated with COVID-19 pathogenesis. In this review, we focus our discussion on recent findings on SARS-CoV-2-induced type I and III IFNs and NLRP3 inflammasome responses and the viral proteins regulating these mechanisms.
Insights into the immune responses of SARS-CoV-2 in relation to COVID-19 vaccines
Heedo Park , Mee Sook Park , Jong Hyeon Seok , Jaehwan You , Jineui Kim , Jeonghun Kim , Man-Seong Park
J. Microbiol. 2022;60(3):308-320.   Published online March 2, 2022
DOI: https://doi.org/10.1007/s12275-022-1598-x
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AbstractAbstract
The three types of approved coronavirus disease 2019 (COVID- 19) vaccines that have been emergency-use listed (EUL) by the World Health Organization are mRNA vaccines, adenovirus- vectored vaccines, and inactivated vaccines. Canonical vaccine developments usually take years or decades to be completed to commercialization; however, the EUL vaccines being used in the current situation comprise several COVID- 19 vaccine candidates applied in studies and clinical settings across the world. The extraordinary circumstances of the COVID-19 pandemic have necessitated the emergency authorization of these EUL vaccines, which have been rapidly developed. Although the benefits of the EUL vaccines outweigh their adverse effects, there have been reports of rare but fatal cases directly associated with COVID-19 vaccinations. Thus, a reassessment of the immunological rationale underlying EUL vaccines in relation to COVID-19 caused by SARSCOV- 2 virus infection is now required. In this review, we discuss the manifestations of COVID-19, immunologically projected effects of EUL vaccines, reported immune responses, informed issues related to COVID-19 vaccination, and the potential strategies for future vaccine use against antigenic variants.
COVID-19 vaccine development based on recombinant viral and bacterial vector systems: combinatorial effect of adaptive and trained immunity
Mi-Hyun Lee , Bum-Joon Kim
J. Microbiol. 2022;60(3):321-334.   Published online February 14, 2022
DOI: https://doi.org/10.1007/s12275-022-1621-2
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AbstractAbstract
Severe acute respiratory syndrome coronavirus 2 virus (SARSCoV- 2) infection, which causes coronavirus disease 2019 (COVID-19), has led to many cases and deaths worldwide. Therefore, a number of vaccine candidates have been developed to control the COVID-19 pandemic. Of these, to date, 21 vaccines have received emergency approval for human use in at least one country. However, the recent global emergence of SARS-CoV-2 variants has compromised the efficacy of the currently available vaccines. To protect against these variants, the use of vaccines that modulate T cell-mediated immune responses or innate immune cell memory function, termed trained immunity, is needed. The major advantage of a vaccine that uses bacteria or viral systems for the delivery of COVID-19 antigens is the ability to induce both T cell-mediated and humoral immune responses. In addition, such vaccine systems can also exert off-target effects via the vector itself, mediated partly through trained immunity; compared to other vaccine platforms, suggesting that this approach can provide better protection against even vaccine escape variants. This review presents the current status of the development of COVID-19 vaccines based on recombinant viral and bacterial delivery systems. We also discuss the current status of the use of licensed live vaccines for other infections, including BCG, oral polio and MMR vaccines, to prevent COVID-19 infections.
Nanoparticle and virus-like particle vaccine approaches against SARS-CoV-2
Chulwoo Kim , Jae-Deog Kim , Sang-Uk Seo
J. Microbiol. 2022;60(3):335-346.   Published online January 28, 2022
DOI: https://doi.org/10.1007/s12275-022-1608-z
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AbstractAbstract
The global spread of coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has provoked an urgent need for prophylactic measures. Several innovative vaccine platforms have been introduced and billions of vaccine doses have been administered worldwide. To enable the creation of safer and more effective vaccines, additional platforms are under development. These include the use of nanoparticle (NP) and virus-like particle (VLP) technology. NP vaccines utilize self-assembling scaffold structures designed to load the entire spike protein or receptor-binding domain of SARS-CoV-2 in a trimeric configuration. In contrast, VLP vaccines are genetically modified recombinant viruses that are considered safe, as they are generally replication-defective. Furthermore, VLPs have indigenous immunogenic potential due to their microbial origin. Importantly, NP and VLP vaccines have shown stronger immunogenicity with greater protection by mimicking the physicochemical characteristics of SARS-CoV-2. The study of NPand VLP-based coronavirus vaccines will help ensure the development of rapid-response technology against SARS-CoV-2 variants and future coronavirus pandemics.
Coronavirus enzyme inhibitors-experimentally proven natural compounds from plants
Junsoo Park , Rackhyun Park , Minsu Jang , Yea-In Park , Yeonjeong Park
J. Microbiol. 2022;60(3):347-354.   Published online January 28, 2022
DOI: https://doi.org/10.1007/s12275-022-1499-z
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AbstractAbstract
Coronavirus disease (COVID-19) can cause critical conditions that require efficient therapeutics. Several medicines are derived from plants, and researchers are seeking natural compounds to ameliorate the symptoms of COVID-19. Viral enzymes are popular targets of antiviral medicines; the genome of coronaviruses encodes several enzymes, including RNAdependent RNA polymerase and viral proteases. Various screening systems have been developed to identify potential inhibitors. In this review, we describe the natural compounds that have been shown to exert inhibitory effects on coronavirus enzymes. Although computer-aided molecular structural studies have predicted several antiviral compound candidates, the current review focuses on experimentally proven natural compounds.

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