Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates

N Engl J Med. 2020 Oct 15;383(16):1544-1555. doi: 10.1056/NEJMoa2024671. Epub 2020 Jul 28.

Abstract

Background: Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important to evaluate in nonhuman primates.

Methods: Nonhuman primates received 10 or 100 μg of mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein of SARS-CoV-2, or no vaccine. Antibody and T-cell responses were assessed before upper- and lower-airway challenge with SARS-CoV-2. Active viral replication and viral genomes in bronchoalveolar-lavage (BAL) fluid and nasal swab specimens were assessed by polymerase chain reaction, and histopathological analysis and viral quantification were performed on lung-tissue specimens.

Results: The mRNA-1273 vaccine candidate induced antibody levels exceeding those in human convalescent-phase serum, with live-virus reciprocal 50% inhibitory dilution (ID50) geometric mean titers of 501 in the 10-μg dose group and 3481 in the 100-μg dose group. Vaccination induced type 1 helper T-cell (Th1)-biased CD4 T-cell responses and low or undetectable Th2 or CD8 T-cell responses. Viral replication was not detectable in BAL fluid by day 2 after challenge in seven of eight animals in both vaccinated groups. No viral replication was detectable in the nose of any of the eight animals in the 100-μg dose group by day 2 after challenge, and limited inflammation or detectable viral genome or antigen was noted in lungs of animals in either vaccine group.

Conclusions: Vaccination of nonhuman primates with mRNA-1273 induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung. (Funded by the National Institutes of Health and others.).

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Betacoronavirus / immunology*
  • Betacoronavirus / physiology
  • CD4 Antigens
  • COVID-19
  • COVID-19 Vaccines
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / pathology
  • Coronavirus Infections / prevention & control*
  • Coronavirus Infections / therapy
  • Disease Models, Animal
  • Dose-Response Relationship, Immunologic
  • Immunization, Passive
  • Lung / pathology
  • Lung / virology
  • Macaca mulatta
  • Pandemics / prevention & control*
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / pathology
  • Pneumonia, Viral / prevention & control*
  • Pneumonia, Viral / therapy
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus
  • T-Lymphocytes / immunology
  • Viral Load
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / immunology*
  • Virus Replication

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • CD4 Antigens
  • COVID-19 Vaccines
  • Spike Glycoprotein, Coronavirus
  • Viral Vaccines
  • spike protein, SARS-CoV-2
  • mRNA-1273 vaccine

Supplementary concepts

  • COVID-19 serotherapy