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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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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.
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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.
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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.
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role of humoral immune responses in COVID-19, primarily
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infections. Though the exact role of T cells in COVID-19 remains
to be elucidated, prior experience with human coronavirus
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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.
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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.
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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.
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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.
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with greater protection by mimicking the physicochemical
characteristics of SARS-CoV-2. The study of NPand
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of rapid-response technology against SARS-CoV-2
variants and future coronavirus pandemics.
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Coronavirus disease (COVID-19) can cause critical conditions
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