AUTHOR=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 TITLE=Intranasal Delivery of MVA Vector Vaccine Induces Effective Pulmonary Immunity Against SARS-CoV-2 in Rodents JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.772240 DOI=10.3389/fimmu.2021.772240 ISSN=1664-3224 ABSTRACT=

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.