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ABSTRACT
Introduction: Middle East respiratory syndrome coronavirus (MERS-CoV) has emerged as a new pathogen, causing severe complications and a high case fatality rate. No direct treatments are available as yet, highlighting the importance of prevention through suitable vaccination regimes. The viral spike (S) protein has been characterized as a key target antigen for vaccines. In particular, S protein domains have been utilized to produce high titers of neutralizing antibodies.
Areas covered: Since the first report of MERS-CoV infection, a limited number of MERS-CoV-specific patents have been filed. Patents related to MERS-CoV are categorized into three areas: treatments, antibodies, and vaccines (receptor-related). This review mainly focuses on the types and efficacies of vaccines, briefly covering treatments and antibodies against the virus. MERS-CoV vaccine forms and delivery systems, together with comparable development strategies against SARS-CoV are additionally addressed.
Expert opinion: Vaccines must be combined with delivery systems, administration routes, and adjuvants to maximize T-cell responses as well as neutralizing antibody production. High immune responses require further study in animal models, such as human receptor-expressing mice, non-human primates, and camels. Such a consideration of integrated actions should contribute to the rapid development of vaccines against MERS-CoV and related coronaviruses.
Article highlights
The main objective is to develop Middle East respiratory syndrome coronavirus (MERS-CoV) vaccines, proteins or fragments that efficiently elicit high levels of neutralizing antibody over a short period of time based on knowledge and understanding of its closely related virus, severe acute respiratory syndrome coronavirus (SARS-CoV).
For protection against infection by a broad range of MERS-CoV variants, DNA vaccines based on consensus DNA sequences of full or partial spike protein (S) have been designed. These DNA sequences have been further modified by including a leader peptide sequence and incorporating codon optimization to ensure stable, high expression of proteins.
Similar to SARS-CoV, a MERS-CoV receptor-binding domain (RBD) in conjunction with Fc is an efficient vaccine that elicits sufficient neutralizing activity, blocking binding of S protein to its receptor, human dipeptidyl peptidase 4 (hDPP4), in the case of MERS-CoV.
S proteins have been formulated in nanoparticles as trimers, which reflect their native conformation on the envelope of MERS-CoV. Nanoparticles mixed with optimal adjuvant are considered potent vaccine candidates. The importance of adjuvants has additionally been addressed.
Viral vectors are attractive delivery tools for vaccines. Owing to their suitable characteristics, such as broad infectivity, including infection of mucosal tissues, adenovirus vaccines in particular have been applied to induce mucosal immunity in addition to T- and B-cell responses.
Modified vaccinia virus Ankara (MVA), a strong immunostimulator, has been employed to express the S protein of MERS-CoV. The resulting vaccine, shown to be capable of inducing significant immune responses, was first administered to camels.
hDPP4-expressing mouse models, which display susceptibility to MERS-CoV infection, have been developed by adenoviral-mediated delivery of hDPP4 or generation of hDPP4 transgenic mice.
While a RBD-based vaccine is suggested as a promising candidate, it is important to consider the combination of efficient immunogens with various delivery systems, adjuvants, and administration routes. Moreover, in the case of DNA and subunit combination vaccines, vaccination sequence is another avenue that should be addressed.
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Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.