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

Immunity. 2021 Mar 9;54(3):542-556.e9. doi: 10.1016/j.immuni.2021.02.001. Epub 2021 Feb 4.

Abstract

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.

Keywords: CD8 T cells; COVID-19; Modified Vaccinia Ankara; Neutralizing antibody; Protection; Rhesus macaques; SARS-CoV-2; Spike; Vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology
  • COVID-19 / immunology
  • COVID-19 / pathology
  • COVID-19 / prevention & control*
  • COVID-19 / virology
  • COVID-19 Vaccines / genetics
  • COVID-19 Vaccines / immunology*
  • Disease Models, Animal
  • Gene Expression
  • Gene Order
  • Genetic Vectors / genetics*
  • Immunophenotyping
  • Lung / immunology
  • Lung / pathology
  • Lung / virology
  • Macaca
  • Macrophages, Alveolar / immunology
  • Macrophages, Alveolar / metabolism
  • Macrophages, Alveolar / pathology
  • Mice
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Vaccination / methods
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*
  • Vaccinia virus / genetics*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Viral
  • COVID-19 Vaccines
  • Spike Glycoprotein, Coronavirus
  • Vaccines, DNA
  • spike protein, SARS-CoV-2