Modified Vaccinia Ankara Vector-Based Vaccine Protects Macaques from SARS-CoV-2 Infection, Immune Pathology and Dysfunction in the Lung

Study show that modified vaccinia Ankara (MVA)-based COVID-19 vaccine expressing membrane anchored pre-fusion stabilized spike (MVA/S) induces both neutralizing antibodies and CD8+ T cells in the blood and lung and protects from SARS-CoV-2 challenge. Single-cell RNA sequencing analysis of lung cells at day 4 post-infection revealed that MVA/S vaccination also protected macaques from infection-induced inflammation and B cell abnormalities, and lowered induction of interferon stimulated genes. To test the immunogenicity and protective ability of the MVA/S vaccine we immunized rhesus macaques (n=5/group) either with MVA/S vaccine or MVA/Wt vaccine delivered intramuscularly on weeks 0 and 4. At week 8 (4 weeks after the boost) animals were challenged intranasally and intratracheally with live SARS-CoV-2 virus. To understand MVA/S vaccine offered inflammatory sequelae in the airway, we performed single-cell RNA-Seq on the cellular fraction recovered from BAL at Day 4 after infection. This analysis shows MVA/S vaccination reduces transcripts associated with inflammation and hyperimmune activation in lung macrophages.