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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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Published in:Frontiers in immunology 2021-11, Vol.12, p.772240-772240
Main Authors: Bošnjak, Berislav, Odak, Ivan, Barros-Martins, Joana, Sandrock, Inga, Hammerschmidt, Swantje I, Permanyer, Marc, Patzer, Gwendolyn E, Greorgiev, Hristo, Gutierrez Jauregui, Rodrigo, Tscherne, Alina, Schwarz, Jan Hendrik, Kalodimou, Georgia, Ssebyatika, George, Ciurkiewicz, Malgorzata, Willenzon, Stefanie, Bubke, Anja, Ristenpart, Jasmin, Ritter, Christiane, Tuchel, Tamara, Meyer Zu Natrup, Christian, Shin, Dai-Lun, Clever, Sabrina, Limpinsel, Leonard, Baumgärtner, Wolfgang, Krey, Thomas, Volz, Asisa, Sutter, Gerd, Förster, Reinhold
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creator Bošnjak, Berislav
Odak, Ivan
Barros-Martins, Joana
Sandrock, Inga
Hammerschmidt, Swantje I
Permanyer, Marc
Patzer, Gwendolyn E
Greorgiev, Hristo
Gutierrez Jauregui, Rodrigo
Tscherne, Alina
Schwarz, Jan Hendrik
Kalodimou, Georgia
Ssebyatika, George
Ciurkiewicz, Malgorzata
Willenzon, Stefanie
Bubke, Anja
Ristenpart, Jasmin
Ritter, Christiane
Tuchel, Tamara
Meyer Zu Natrup, Christian
Shin, Dai-Lun
Clever, Sabrina
Limpinsel, Leonard
Baumgärtner, Wolfgang
Krey, Thomas
Volz, Asisa
Sutter, Gerd
Förster, Reinhold
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.
doi_str_mv 10.3389/fimmu.2021.772240
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subjects Administration, Intranasal
Animals
Antibodies, Neutralizing - blood
Antibodies, Viral - blood
bronchus-associated lymphoid tissue (BALT)
CD8-Positive T-Lymphocytes - immunology
Cell Line
Chlorocebus aethiops
COVID-19 - prevention & control
COVID-19 Vaccines - immunology
Cricetinae
Genetic Vectors
Immunization, Secondary
Immunoglobulin A - blood
Immunoglobulin G - blood
Immunology
Lung - immunology
lungs
Male
Mice
Mice, Inbred C57BL
modified vaccinia virus Ankara (MVA)
SARS-CoV-2 - immunology
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
spike (S) protein
Spike Glycoprotein, Coronavirus - immunology
Th1 Cells - immunology
Vaccination
vaccine
Vaccines, Subunit - immunology
Vaccinia virus - immunology
Vero Cells
Viral Load - immunology
title Intranasal Delivery of MVA Vector Vaccine Induces Effective Pulmonary Immunity Against SARS-CoV-2 in Rodents
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