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

• 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
• Format: Article
• Language: English
• 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
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.772240

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.