Immunogenicity and efficacy of a novel multi-patch SARS-CoV-2/COVID-19 vaccine candidate

Abstract

IntroductionWhile there has been considerable progress in the development of vaccines against SARS-CoV-2, largely based on the S (spike) protein of the virus, less progress has been made with vaccines delivering different viral antigens with cross-reactive potential.MethodsIn an effort to develop an immunogen with the capacity to induce broad antigen presentation, we have designed a multi-patch synthetic candidate containing dominant and persistent B cell epitopes from conserved regions of SARS-CoV-2 structural proteins associated with long-term immunity, termed CoV2-BMEP. Here we describe the characterization, immunogenicity and efficacy of CoV2-BMEP using two delivery platforms: nucleic acid DNA and attenuated modified vaccinia virus Ankara (MVA).ResultsIn cultured cells, both vectors produced a main protein of about 37 kDa as well as heterogeneous proteins with size ranging between 25-37 kDa. In C57BL/6 mice, both homologous and heterologous prime/boost combination of vectors induced the activation of SARS-CoV-2-specific CD4 and CD8 T cell responses, with a more balanced CD8+ T cell response detected in lungs. The homologous MVA/MVA immunization regimen elicited the highest specific CD8+ T cell responses in spleen and detectable binding antibodies (bAbs) to S and N antigens of SARS-CoV-2. In SARS-CoV-2 susceptible k18-hACE2 Tg mice, two doses of MVA-CoV2-BMEP elicited S- and N-specific bAbs as well as cross-neutralizing antibodies against different variants of concern (VoC). After SARS-CoV-2 challenge, all animals in the control unvaccinated group succumbed to the infection while vaccinated animals with high titers of neutralizing antibodies were fully protected against mortality, correlating with a reduction of virus infection in the lungs and inhibition of the cytokine storm.DiscussionThese findings revealed a novel immunogen with the capacity to control SARS-CoV-2 infection, using a broader antigen presentation mechanism than the approved vaccines based solely on the S antigen.

Rendezvous with Vaccinia Virus in the Post-smallpox Era: R&D Advances

“…Plentiful studies target arboviruses that are on the rise: dengue virus [ 161 ], Zika virus [ 50 , 162 , 163 , 164 , 165 ], West Nile virus [ 166 ], yellow fever virus [ 167 ], tick-borne encephalitis virus [ 168 , 169 ], chikungunya virus [ 163 , 170 ], and Crimean-Congo hemorrhagic fever virus [ 171 ]. Multiple diseases of high prevalence or fatality rate, especially those with epidemic or pandemic potential garner particular attention, including the following examples: ebolavirus [ 172 , 173 , 174 , 175 ], Nipah virus [ 176 ], influenza virus [ 177 , 178 , 179 , 180 ], respiratory syncytial virus [ 181 , 182 ], Middle East respiratory syndrome coronavirus [ 183 , 184 ], and needless to say, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [ 158 , 185 , 186 , 187 , 188 , 189 , 190 , 191 , 192 , 193 , 194 , 195 ]. Several VACV-vectored vaccines have entered clinical trials: HIV-1 [ 196 ], tuberculosis [ 197 , 198 ], respiratory syncytial virus [ 199 ], influenza A virus [ 200 ], and SARS-CoV-2 [ 201 ].…”