| First Author | Perdiguero B | Year | 2023 |
| Journal | Front Immunol | Volume | 14 |
| Pages | 1160065 | PubMed ID | 37404819 |
| Mgi Jnum | J:337764 | Mgi Id | MGI:7505942 |
| Doi | 10.3389/fimmu.2023.1160065 | Citation | Perdiguero B, et al. (2023) Immunogenicity and efficacy of a novel multi-patch SARS-CoV-2/COVID-19 vaccine candidate. Front Immunol 14:1160065 |
| abstractText | INTRODUCTION: While 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. METHODS: In 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). RESULTS: In 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. DISCUSSION: These 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. |
