6. Conclusions and perspectives
Development of effective vaccines is urgently needed to control
the spread of emerging MERS-CoV infections. While viral vector based and live-attenuated virus-based vaccines have potential for
providing effective immunity, subunit vaccines will offer the safest
means for prevention. Although subunit-based vaccines might
induce less immunogenicity than the other vaccine types, their efficacy can be significantly improved by rational design based on the
structural analysis of RBD of MERS-CoV S protein and by identification of the most stable and critical neutralizing fragment of RBD,
while eliminating non-neutralizing epitopes through immunofocusing (Ma et al., 2014b). Overall, our strategies in the development
of MERS-CoV RBD-based subunit vaccines will provide useful information for the design of effective vaccines against MERS-CoV and
any other emerging coronaviruses that might cause future pandemics. It is expected that such developed MERS candidate vaccines
will be tested for efficacy in preventing MERS-CoV infections in vivo
once affordable small animal models for MERS-CoV have become
available. Because serologic and neutralization responses against S
proteins of MERS-CoV, SARS-CoV and other coronaviruses share no,
to low, levels of cross-reactivity within and/or across subgroups,
it is advisable that MERS-CoV and other coronavirus vaccines be
designed by considering construction ofchimeric S protein containing neutralizing epitopes from variant virus strains (Agnihothram
et al., 2014).
Conflict of interest statement
The authors declared no conflict of interest.
158 N. Zhang et al. / Virus Research 202 (2015) 151–159
Acknowledgments
This study was supported by NIH grant (R21AI109094). We
thank Yang Yang at the Department of Pharmacology, University of
Minnesota Medical School, for the structural analysis of SARS-CoV
and MERS-CoV RBDs.
6. Conclusions and perspectivesDevelopment of effective vaccines is urgently needed to controlthe spread of emerging MERS-CoV infections. While viral vector based and live-attenuated virus-based vaccines have potential forproviding effective immunity, subunit vaccines will offer the safestmeans for prevention. Although subunit-based vaccines mightinduce less immunogenicity than the other vaccine types, their efficacy can be significantly improved by rational design based on thestructural analysis of RBD of MERS-CoV S protein and by identification of the most stable and critical neutralizing fragment of RBD,while eliminating non-neutralizing epitopes through immunofocusing (Ma et al., 2014b). Overall, our strategies in the developmentof MERS-CoV RBD-based subunit vaccines will provide useful information for the design of effective vaccines against MERS-CoV andany other emerging coronaviruses that might cause future pandemics. It is expected that such developed MERS candidate vaccineswill be tested for efficacy in preventing MERS-CoV infections in vivoonce affordable small animal models for MERS-CoV have becomeavailable. Because serologic and neutralization responses against Sproteins of MERS-CoV, SARS-CoV and other coronaviruses share no,to low, levels of cross-reactivity within and/or across subgroups,it is advisable that MERS-CoV and other coronavirus vaccines bedesigned by considering construction ofchimeric S protein containing neutralizing epitopes from variant virus strains (Agnihothramet al., 2014).Conflict of interest statementThe authors declared no conflict of interest.158 N. Zhang et al. / Virus Research 202 (2015) 151–159AcknowledgmentsThis study was supported by NIH grant (R21AI109094). Wethank Yang Yang at the Department of Pharmacology, University ofMinnesota Medical School, for the structural analysis of SARS-CoVand MERS-CoV RBDs.
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