Intranasal Delivery of MVA Vector Vaccine Induces Effective Pulmonary Immunity Against SARS-CoV-2 in Rodents

Berislav Bošnjak*, Ivan Odak, Joana Barros-Martins, Inga Sandrock, Swantje I. Hammerschmidt, Marc Permanyer, Gwendolyn E. Patzer, Hristo Greorgiev, Rodrigo Gutierrez Jauregui, Alina Tscherne, Jan Hendrik Schwarz, Georgia Kalodimou, George Ssebyatika, Malgorzata Ciurkiewicz, Stefanie Willenzon, Anja Bubke, Jasmin Ristenpart, Christiane Ritter, Tamara Tuchel, Christian Meyer zu NatrupDai Lun Shin, Sabrina Clever, Leonard Limpinsel, Wolfgang Baumgärtner, Thomas Krey, Asisa Volz, Gerd Sutter, Reinhold Förster

*Corresponding author for this work


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.

Original languageEnglish
Article number772240
JournalFrontiers in Immunology
Publication statusPublished - 11.11.2021


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