Frontiers in Immunology (Nov 2021)

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,
  • 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

DOI
https://doi.org/10.3389/fimmu.2021.772240
Journal volume & issue
Vol. 12

Abstract

Read online

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.

Keywords