A modified vaccinia Ankara vector-based vaccine protects macaques from SARS-CoV-2 infection, immune pathology, and dysfunction in the lungs.
A combination of vaccination approaches will likely be necessary to fully control the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Here, we show that modified vaccinia Ankara (MVA) vectors expressing membrane-anchored pre-fusion stabilized spike (MVA/S) but not secreted S1 induced strong neutralizing antibody responses against SARS-CoV-2 in mice. In macaques, the MVA/S vaccination induced strong neutralizing antibodies and CD8+ T cell responses, and conferred protection from SARS-CoV-2 infection and virus replication in the lungs as early as day 2 following intranasal and intratracheal challenge. Single-cell RNA sequencing analysis of lung cells on day 4 after infection revealed that MVA/S vaccination also protected macaques from infection-induced inflammation and B cell abnormalities and lowered induction of interferon-stimulated genes. These results demonstrate that MVA/S vaccination induces neutralizing antibodies and CD8+ T cells in the blood and lungs and is a potential vaccine candidate for SARS-CoV-2.
Routhu, NK; Cheedarla, N; Gangadhara, S; Bollimpelli, VS; Boddapati, AK; Shiferaw, A; Rahman, SA; Sahoo, A; Edara, VV; Lai, L; Floyd, K; Wang, S; Fischinger, S; Atyeo, C; Shin, SA; Gumber, S; Kirejczyk, S; Cohen, J; Jean, SM; Wood, JS; Connor-Stroud, F; Stammen, RL; Upadhyay, AA; Pellegrini, K; Montefiori, D; Shi, P-Y; Menachery, VD; Alter, G; Vanderford, TH; Bosinger, SE; Suthar, MS; Amara, RR
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