A modified vaccinia Ankara vector-based vaccine protects macaques from SARS-CoV-2 infection, immune pathology, and dysfunction in the lungs.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • March 9, 2021

Published In

Volume / Issue

  • 54 / 3

Start / End Page

  • 542 - 556.e9

PubMed ID

  • 33631118

Pubmed Central ID

  • PMC7859620

Electronic International Standard Serial Number (EISSN)

  • 1097-4180

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2021.02.001

Language

  • eng

Conference Location

  • United States