Immunogenicity and efficacy of a novel multi-patch SARS-CoV-2/COVID-19 vaccine candidate
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1160065/full |
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| author | Beatriz Perdiguero Beatriz Perdiguero Laura Marcos-Villar María López-Bravo Pedro J. Sánchez-Cordón Carmen Zamora José Ramón Valverde Carlos Óscar S. Sorzano Laura Sin Enrique Álvarez Manuel Ramos Margarita Del Val Mariano Esteban Carmen Elena Gómez Carmen Elena Gómez |
| author_facet | Beatriz Perdiguero Beatriz Perdiguero Laura Marcos-Villar María López-Bravo Pedro J. Sánchez-Cordón Carmen Zamora José Ramón Valverde Carlos Óscar S. Sorzano Laura Sin Enrique Álvarez Manuel Ramos Margarita Del Val Mariano Esteban Carmen Elena Gómez Carmen Elena Gómez |
| author_sort | Beatriz Perdiguero |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T04:31:13Z |
| format | Article |
| id | doaj.art-aab6f6a61ca44a0492001c9d0e3ba5a9 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T04:31:13Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-aab6f6a61ca44a0492001c9d0e3ba5a92023-06-19T13:32:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-06-011410.3389/fimmu.2023.11600651160065Immunogenicity and efficacy of a novel multi-patch SARS-CoV-2/COVID-19 vaccine candidateBeatriz Perdiguero0Beatriz Perdiguero1Laura Marcos-Villar2María López-Bravo3Pedro J. Sánchez-Cordón4Carmen Zamora5José Ramón Valverde6Carlos Óscar S. Sorzano7Laura Sin8Enrique Álvarez9Manuel Ramos10Margarita Del Val11Mariano Esteban12Carmen Elena Gómez13Carmen Elena Gómez14Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, SpainDepartment of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, SpainDepartment of Microbial Biotechnology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, SpainVeterinary Pathology Department, Centro de Investigación en Sanidad Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Consejo Superior de Investigaciones Científicas, Madrid, SpainDepartment of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, SpainScientific Computing, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, SpainBiocomputing Unit and Computational Genomics, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, SpainCentro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, SpainCentro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, SpainDepartment of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, SpainDepartment of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, SpainIntroductionWhile 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1160065/fullSARS-CoV-2multi-patch vaccinepoxvirus MVAmice studiesB and T cell immune responsesbinding and neutralizing antibodies |
| spellingShingle | Beatriz Perdiguero Beatriz Perdiguero Laura Marcos-Villar María López-Bravo Pedro J. Sánchez-Cordón Carmen Zamora José Ramón Valverde Carlos Óscar S. Sorzano Laura Sin Enrique Álvarez Manuel Ramos Margarita Del Val Mariano Esteban Carmen Elena Gómez Carmen Elena Gómez Immunogenicity and efficacy of a novel multi-patch SARS-CoV-2/COVID-19 vaccine candidate Frontiers in Immunology SARS-CoV-2 multi-patch vaccine poxvirus MVA mice studies B and T cell immune responses binding and neutralizing antibodies |
| title | Immunogenicity and efficacy of a novel multi-patch SARS-CoV-2/COVID-19 vaccine candidate |
| title_full | Immunogenicity and efficacy of a novel multi-patch SARS-CoV-2/COVID-19 vaccine candidate |
| title_fullStr | Immunogenicity and efficacy of a novel multi-patch SARS-CoV-2/COVID-19 vaccine candidate |
| title_full_unstemmed | Immunogenicity and efficacy of a novel multi-patch SARS-CoV-2/COVID-19 vaccine candidate |
| title_short | Immunogenicity and efficacy of a novel multi-patch SARS-CoV-2/COVID-19 vaccine candidate |
| title_sort | immunogenicity and efficacy of a novel multi patch sars cov 2 covid 19 vaccine candidate |
| topic | SARS-CoV-2 multi-patch vaccine poxvirus MVA mice studies B and T cell immune responses binding and neutralizing antibodies |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1160065/full |
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