Early protective effect of a (“pan”) coronavirus vaccine (PanCoVac) in Roborovski dwarf hamsters after single-low dose intranasal administration
IntroductionThe coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the danger posed by human coronaviruses. Rapid emergence of immunoevasive variants and waning antiviral immunity decrease the effect of the currently av...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1166765/full |
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| author | Mohammed O. Abdelaziz Mohammed O. Abdelaziz Martin J. Raftery Martin J. Raftery Martin J. Raftery Julian Weihs Julian Weihs Olivia Bielawski Richard Edel Julia Köppke Daria Vladimirova Julia M. Adler Theresa Firsching Anne Voß Achim D. Gruber Luca V. Hummel Ivan Fernandez Munoz Francesca Müller-Marquardt Gerald Willimsky Gerald Willimsky Gerald Willimsky Nooran S. Elleboudy Nooran S. Elleboudy Jakob Trimpert Günther Schönrich |
| author_facet | Mohammed O. Abdelaziz Mohammed O. Abdelaziz Martin J. Raftery Martin J. Raftery Martin J. Raftery Julian Weihs Julian Weihs Olivia Bielawski Richard Edel Julia Köppke Daria Vladimirova Julia M. Adler Theresa Firsching Anne Voß Achim D. Gruber Luca V. Hummel Ivan Fernandez Munoz Francesca Müller-Marquardt Gerald Willimsky Gerald Willimsky Gerald Willimsky Nooran S. Elleboudy Nooran S. Elleboudy Jakob Trimpert Günther Schönrich |
| author_sort | Mohammed O. Abdelaziz |
| collection | DOAJ |
| description | IntroductionThe coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the danger posed by human coronaviruses. Rapid emergence of immunoevasive variants and waning antiviral immunity decrease the effect of the currently available vaccines, which aim at induction of neutralizing antibodies. In contrast, T cells are marginally affected by antigen evolution although they represent the major mediators of virus control and vaccine protection against virus-induced disease.Materials and methodsWe generated a multi-epitope vaccine (PanCoVac) that encodes the conserved T cell epitopes from all structural proteins of coronaviruses. PanCoVac contains elements that facilitate efficient processing and presentation of PanCoVac-encoded T cell epitopes and can be uploaded to any available vaccine platform. For proof of principle, we cloned PanCoVac into a non-integrating lentivirus vector (NILV-PanCoVac). We chose Roborovski dwarf hamsters for a first step in evaluating PanCoVac in vivo. Unlike mice, they are naturally susceptible to SARS-CoV-2 infection. Moreover, Roborovski dwarf hamsters develop COVID-19-like disease after infection with SARS-CoV-2 enabling us to look at pathology and clinical symptoms.ResultsUsing HLA-A*0201-restricted reporter T cells and U251 cells expressing a tagged version of PanCoVac, we confirmed in vitro that PanCoVac is processed and presented by HLA-A*0201. As mucosal immunity in the respiratory tract is crucial for protection against respiratory viruses such as SARS-CoV-2, we tested the protective effect of single-low dose of NILV-PanCoVac administered via the intranasal (i.n.) route in the Roborovski dwarf hamster model of COVID-19. After infection with ancestral SARS-CoV-2, animals immunized with a single-low dose of NILV-PanCoVac i.n. did not show symptoms and had significantly decreased viral loads in the lung tissue. This protective effect was observed in the early phase (2 days post infection) after challenge and was not dependent on neutralizing antibodies.ConclusionPanCoVac, a multi-epitope vaccine covering conserved T cell epitopes from all structural proteins of coronaviruses, might protect from severe disease caused by SARS-CoV-2 variants and future pathogenic coronaviruses. The use of (HLA-) humanized animal models will allow for further efficacy studies of PanCoVac-based vaccines in vivo. |
| first_indexed | 2024-03-13T00:01:19Z |
| format | Article |
| id | doaj.art-c6aaf49ce07547e3a2fd4dc32b8a59b3 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T00:01:19Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c6aaf49ce07547e3a2fd4dc32b8a59b32023-07-13T11:33:21ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-07-011410.3389/fimmu.2023.11667651166765Early protective effect of a (“pan”) coronavirus vaccine (PanCoVac) in Roborovski dwarf hamsters after single-low dose intranasal administrationMohammed O. Abdelaziz0Mohammed O. Abdelaziz1Martin J. Raftery2Martin J. Raftery3Martin J. Raftery4Julian Weihs5Julian Weihs6Olivia Bielawski7Richard Edel8Julia Köppke9Daria Vladimirova10Julia M. Adler11Theresa Firsching12Anne Voß13Achim D. Gruber14Luca V. Hummel15Ivan Fernandez Munoz16Francesca Müller-Marquardt17Gerald Willimsky18Gerald Willimsky19Gerald Willimsky20Nooran S. Elleboudy21Nooran S. Elleboudy22Jakob Trimpert23Günther Schönrich24Institute of Virology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, GermanyBerlin Institute of Health, Charité – Universitätsmedizin Berlin, Berlin, GermanyInstitute of Virology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, GermanyBerlin Institute of Health, Charité – Universitätsmedizin Berlin, Berlin, GermanyDepartment of Hematology, Oncology and Tumor Immunology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, GermanyInstitute of Virology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, GermanyDepartment of Pediatrics, Division of Gastroenterology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, GermanyInstitute of Virology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, GermanyInstitute of Virology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, GermanyInstitute of Virology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, GermanyInstitute of Virology, Freie Universität Berlin, Berlin, GermanyInstitute of Virology, Freie Universität Berlin, Berlin, GermanyInstitute of Veterinary Pathology, Freie Universität Berlin, Berlin, GermanyInstitute of Veterinary Pathology, Freie Universität Berlin, Berlin, GermanyInstitute of Veterinary Pathology, Freie Universität Berlin, Berlin, GermanyInstitute of Virology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, GermanyInstitute of Virology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, GermanyInstitute of Virology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, GermanyInstitute of Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, GermanyGerman Cancer Research Center, Heidelberg, GermanyGerman Cancer Consortium, Partner Site Berlin, Berlin, GermanyInstitute of Virology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany0Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University, Cairo, EgyptInstitute of Virology, Freie Universität Berlin, Berlin, GermanyInstitute of Virology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, GermanyIntroductionThe coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the danger posed by human coronaviruses. Rapid emergence of immunoevasive variants and waning antiviral immunity decrease the effect of the currently available vaccines, which aim at induction of neutralizing antibodies. In contrast, T cells are marginally affected by antigen evolution although they represent the major mediators of virus control and vaccine protection against virus-induced disease.Materials and methodsWe generated a multi-epitope vaccine (PanCoVac) that encodes the conserved T cell epitopes from all structural proteins of coronaviruses. PanCoVac contains elements that facilitate efficient processing and presentation of PanCoVac-encoded T cell epitopes and can be uploaded to any available vaccine platform. For proof of principle, we cloned PanCoVac into a non-integrating lentivirus vector (NILV-PanCoVac). We chose Roborovski dwarf hamsters for a first step in evaluating PanCoVac in vivo. Unlike mice, they are naturally susceptible to SARS-CoV-2 infection. Moreover, Roborovski dwarf hamsters develop COVID-19-like disease after infection with SARS-CoV-2 enabling us to look at pathology and clinical symptoms.ResultsUsing HLA-A*0201-restricted reporter T cells and U251 cells expressing a tagged version of PanCoVac, we confirmed in vitro that PanCoVac is processed and presented by HLA-A*0201. As mucosal immunity in the respiratory tract is crucial for protection against respiratory viruses such as SARS-CoV-2, we tested the protective effect of single-low dose of NILV-PanCoVac administered via the intranasal (i.n.) route in the Roborovski dwarf hamster model of COVID-19. After infection with ancestral SARS-CoV-2, animals immunized with a single-low dose of NILV-PanCoVac i.n. did not show symptoms and had significantly decreased viral loads in the lung tissue. This protective effect was observed in the early phase (2 days post infection) after challenge and was not dependent on neutralizing antibodies.ConclusionPanCoVac, a multi-epitope vaccine covering conserved T cell epitopes from all structural proteins of coronaviruses, might protect from severe disease caused by SARS-CoV-2 variants and future pathogenic coronaviruses. The use of (HLA-) humanized animal models will allow for further efficacy studies of PanCoVac-based vaccines in vivo.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1166765/fulluniversal COVID-19 vaccinecoronavirusesmulti-epitope vaccineT cell epitopespan-coronavirus vaccinedwarf hamster COVID-19 model |
| spellingShingle | Mohammed O. Abdelaziz Mohammed O. Abdelaziz Martin J. Raftery Martin J. Raftery Martin J. Raftery Julian Weihs Julian Weihs Olivia Bielawski Richard Edel Julia Köppke Daria Vladimirova Julia M. Adler Theresa Firsching Anne Voß Achim D. Gruber Luca V. Hummel Ivan Fernandez Munoz Francesca Müller-Marquardt Gerald Willimsky Gerald Willimsky Gerald Willimsky Nooran S. Elleboudy Nooran S. Elleboudy Jakob Trimpert Günther Schönrich Early protective effect of a (“pan”) coronavirus vaccine (PanCoVac) in Roborovski dwarf hamsters after single-low dose intranasal administration Frontiers in Immunology universal COVID-19 vaccine coronaviruses multi-epitope vaccine T cell epitopes pan-coronavirus vaccine dwarf hamster COVID-19 model |
| title | Early protective effect of a (“pan”) coronavirus vaccine (PanCoVac) in Roborovski dwarf hamsters after single-low dose intranasal administration |
| title_full | Early protective effect of a (“pan”) coronavirus vaccine (PanCoVac) in Roborovski dwarf hamsters after single-low dose intranasal administration |
| title_fullStr | Early protective effect of a (“pan”) coronavirus vaccine (PanCoVac) in Roborovski dwarf hamsters after single-low dose intranasal administration |
| title_full_unstemmed | Early protective effect of a (“pan”) coronavirus vaccine (PanCoVac) in Roborovski dwarf hamsters after single-low dose intranasal administration |
| title_short | Early protective effect of a (“pan”) coronavirus vaccine (PanCoVac) in Roborovski dwarf hamsters after single-low dose intranasal administration |
| title_sort | early protective effect of a pan coronavirus vaccine pancovac in roborovski dwarf hamsters after single low dose intranasal administration |
| topic | universal COVID-19 vaccine coronaviruses multi-epitope vaccine T cell epitopes pan-coronavirus vaccine dwarf hamster COVID-19 model |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1166765/full |
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