A decade ago, severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) caused a global pandemic with a mortality rate of 10%. Reports of recent outbreaks of a SARS-like disease caused by Middle East respiratory syndrome coronavirus (MERS-CoV) have raised serious concerns of a possible reemergence of SARS-CoV, either by laboratory escape or the presence of a natural reservoir. Therefore, the development of effective and safe SARS vaccines is still needed. Based on our previous studies, we believe that the receptor-binding domain (RBD) in the S1 subunit of the SARS-CoV spike (S) protein is the most important target for developing a SARS vaccine. In particular, RBD of S protein contains the critical neutralizing domain (CND), which is able to induce highly potent neutralizing antibody response and cross-protection against divergent SARS-CoV strains. Furthermore, a RBD-based subunit vaccine is expected to be safer than other vaccines that may induce Th2-type immunopathology. This review will discuss key advances in the development of RBD-based SARS vaccines and the possibility of using a similar strategy to develop vaccines against MERS-CoV.
Conclusions and prospect
Considering the recent outbreaks of SARS-like disease caused by the newly emerged MERS-CoV and the potential of future recurrence of SARS, development of effective and safe vaccines against SARS-CoV remains a high priority. Our previous studies have demonstrated that the RBD in the S1 subunit of the SARS-CoV S protein contains the CND that can induce highly potent humoral and cellular immune responses, particularly cross-neutralizing antibodies and strong protective immunity. Therefore, RBD-based vaccines show considerable promise for further development as a highly effective SARS vaccine. Furthermore, this strategy could also be employed for the development of vaccines against other emerging infectious diseases caused by enveloped viruses with class I membrane fusion proteins, such as avian influenza A(H7N9) virus (41-43) and MERS-CoV (7,24). Recently, Chan et al. (44) have demonstrated that sera collected from convalescent SARS patients may contain crossreactive antibodies against MERS-CoV detected by both immunofluorescent and neutralizing antibody tests. Based on bioinformatics analysis, they anticipated that the B-cell epitope that elicited cross-reactive antibodies may be located in the S2 subunit HR2 domain of MERS-CoV. Most recently, we have shown that the mAbs specific for the RBD of SARS-CoV S protein exhibited no cross-reactive or cross-neutralizing activity against MERS-CoV, suggesting that the RBDs of SARS-CoV and MERS-CoV S proteins may not contain the epitopes for inducing cross-reactive antibody responses (45). Therefore, the design and development of a RBD-based vaccine against MERSCoV will need to follow an experimental path similar to that of our RBD-based SARS vaccine.
Reference & source information: http://jtd.amegroups.com/
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