Intranasal Delivery of MVA Vector Vaccine Induces Effective Pulmonary Immunity Against SARS-CoV-2 in Rodents
Antigen-specific tissue-resident memory T cells (Trms) and neutralizing IgA antibodies provide the most effective protection of the lungs from viral infections. To induce those essential components of lung immunity against SARS-CoV-2, we tested various immunization protocols involving intranasal del...
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2021
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oai:doaj.org-article:76eb9b3576254d289905045704455f622021-11-11T10:23:20ZIntranasal Delivery of MVA Vector Vaccine Induces Effective Pulmonary Immunity Against SARS-CoV-2 in Rodents1664-322410.3389/fimmu.2021.772240https://doaj.org/article/76eb9b3576254d289905045704455f622021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.772240/fullhttps://doaj.org/toc/1664-3224Antigen-specific tissue-resident memory T cells (Trms) and neutralizing IgA antibodies provide the most effective protection of the lungs from viral infections. To induce those essential components of lung immunity against SARS-CoV-2, we tested various immunization protocols involving intranasal delivery of a novel Modified Vaccinia virus Ankara (MVA)-SARS-2-spike vaccine candidate. We show that a single intranasal MVA-SARS-CoV-2-S application in mice strongly induced pulmonary spike-specific CD8+ T cells, albeit restricted production of neutralizing antibodies. In prime-boost protocols, intranasal booster vaccine delivery proved to be crucial for a massive expansion of systemic and lung tissue-resident spike-specific CD8+ T cells and the development of Th1 - but not Th2 - CD4+ T cells. Likewise, very high titers of IgG and IgA anti-spike antibodies were present in serum and broncho-alveolar lavages that possessed high virus neutralization capacities to all current SARS-CoV-2 variants of concern. Importantly, the MVA-SARS-2-spike vaccine applied in intramuscular priming and intranasal boosting treatment regimen completely protected hamsters from developing SARS-CoV-2 lung infection and pathology. Together, these results identify intramuscular priming followed by respiratory tract boosting with MVA-SARS-2-S as a promising approach for the induction of local, respiratory as well as systemic immune responses suited to protect from SARS-CoV-2 infections.Berislav BošnjakIvan OdakJoana Barros-MartinsInga SandrockSwantje I. HammerschmidtMarc PermanyerGwendolyn E. PatzerHristo GreorgievRodrigo Gutierrez JaureguiAlina TscherneAlina TscherneJan Hendrik SchwarzGeorgia KalodimouGeorgia KalodimouGeorge SsebyatikaMalgorzata CiurkiewiczStefanie WillenzonAnja BubkeJasmin RistenpartChristiane RitterTamara TuchelChristian Meyer zu NatrupDai-Lun ShinSabrina CleverLeonard LimpinselWolfgang BaumgärtnerThomas KreyThomas KreyThomas KreyThomas KreyThomas KreyAsisa VolzAsisa VolzAsisa VolzGerd SutterGerd SutterReinhold FörsterReinhold FörsterReinhold FörsterFrontiers Media S.A.articlebronchus-associated lymphoid tissue (BALT)lungsmodified vaccinia virus Ankara (MVA)severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)spike (S) proteinvaccineImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
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DOAJ |
| collection |
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EN |
| topic |
bronchus-associated lymphoid tissue (BALT) lungs modified vaccinia virus Ankara (MVA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein vaccine Immunologic diseases. Allergy RC581-607 |
| spellingShingle |
bronchus-associated lymphoid tissue (BALT) lungs modified vaccinia virus Ankara (MVA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein vaccine Immunologic diseases. Allergy RC581-607 Berislav Bošnjak Ivan Odak Joana Barros-Martins Inga Sandrock Swantje I. Hammerschmidt Marc Permanyer Gwendolyn E. Patzer Hristo Greorgiev Rodrigo Gutierrez Jauregui Alina Tscherne Alina Tscherne Jan Hendrik Schwarz Georgia Kalodimou Georgia Kalodimou George Ssebyatika Malgorzata Ciurkiewicz Stefanie Willenzon Anja Bubke Jasmin Ristenpart Christiane Ritter Tamara Tuchel Christian Meyer zu Natrup Dai-Lun Shin Sabrina Clever Leonard Limpinsel Wolfgang Baumgärtner Thomas Krey Thomas Krey Thomas Krey Thomas Krey Thomas Krey Asisa Volz Asisa Volz Asisa Volz Gerd Sutter Gerd Sutter Reinhold Förster Reinhold Förster Reinhold Förster Intranasal Delivery of MVA Vector Vaccine Induces Effective Pulmonary Immunity Against SARS-CoV-2 in Rodents |
| description |
Antigen-specific tissue-resident memory T cells (Trms) and neutralizing IgA antibodies provide the most effective protection of the lungs from viral infections. To induce those essential components of lung immunity against SARS-CoV-2, we tested various immunization protocols involving intranasal delivery of a novel Modified Vaccinia virus Ankara (MVA)-SARS-2-spike vaccine candidate. We show that a single intranasal MVA-SARS-CoV-2-S application in mice strongly induced pulmonary spike-specific CD8+ T cells, albeit restricted production of neutralizing antibodies. In prime-boost protocols, intranasal booster vaccine delivery proved to be crucial for a massive expansion of systemic and lung tissue-resident spike-specific CD8+ T cells and the development of Th1 - but not Th2 - CD4+ T cells. Likewise, very high titers of IgG and IgA anti-spike antibodies were present in serum and broncho-alveolar lavages that possessed high virus neutralization capacities to all current SARS-CoV-2 variants of concern. Importantly, the MVA-SARS-2-spike vaccine applied in intramuscular priming and intranasal boosting treatment regimen completely protected hamsters from developing SARS-CoV-2 lung infection and pathology. Together, these results identify intramuscular priming followed by respiratory tract boosting with MVA-SARS-2-S as a promising approach for the induction of local, respiratory as well as systemic immune responses suited to protect from SARS-CoV-2 infections. |
| format |
article |
| author |
Berislav Bošnjak Ivan Odak Joana Barros-Martins Inga Sandrock Swantje I. Hammerschmidt Marc Permanyer Gwendolyn E. Patzer Hristo Greorgiev Rodrigo Gutierrez Jauregui Alina Tscherne Alina Tscherne Jan Hendrik Schwarz Georgia Kalodimou Georgia Kalodimou George Ssebyatika Malgorzata Ciurkiewicz Stefanie Willenzon Anja Bubke Jasmin Ristenpart Christiane Ritter Tamara Tuchel Christian Meyer zu Natrup Dai-Lun Shin Sabrina Clever Leonard Limpinsel Wolfgang Baumgärtner Thomas Krey Thomas Krey Thomas Krey Thomas Krey Thomas Krey Asisa Volz Asisa Volz Asisa Volz Gerd Sutter Gerd Sutter Reinhold Förster Reinhold Förster Reinhold Förster |
| author_facet |
Berislav Bošnjak Ivan Odak Joana Barros-Martins Inga Sandrock Swantje I. Hammerschmidt Marc Permanyer Gwendolyn E. Patzer Hristo Greorgiev Rodrigo Gutierrez Jauregui Alina Tscherne Alina Tscherne Jan Hendrik Schwarz Georgia Kalodimou Georgia Kalodimou George Ssebyatika Malgorzata Ciurkiewicz Stefanie Willenzon Anja Bubke Jasmin Ristenpart Christiane Ritter Tamara Tuchel Christian Meyer zu Natrup Dai-Lun Shin Sabrina Clever Leonard Limpinsel Wolfgang Baumgärtner Thomas Krey Thomas Krey Thomas Krey Thomas Krey Thomas Krey Asisa Volz Asisa Volz Asisa Volz Gerd Sutter Gerd Sutter Reinhold Förster Reinhold Förster Reinhold Förster |
| author_sort |
Berislav Bošnjak |
| title |
Intranasal Delivery of MVA Vector Vaccine Induces Effective Pulmonary Immunity Against SARS-CoV-2 in Rodents |
| title_short |
Intranasal Delivery of MVA Vector Vaccine Induces Effective Pulmonary Immunity Against SARS-CoV-2 in Rodents |
| title_full |
Intranasal Delivery of MVA Vector Vaccine Induces Effective Pulmonary Immunity Against SARS-CoV-2 in Rodents |
| title_fullStr |
Intranasal Delivery of MVA Vector Vaccine Induces Effective Pulmonary Immunity Against SARS-CoV-2 in Rodents |
| title_full_unstemmed |
Intranasal Delivery of MVA Vector Vaccine Induces Effective Pulmonary Immunity Against SARS-CoV-2 in Rodents |
| title_sort |
intranasal delivery of mva vector vaccine induces effective pulmonary immunity against sars-cov-2 in rodents |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/76eb9b3576254d289905045704455f62 |
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