Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses

Nature. 2021 Jun;594(7864):553-559. doi: 10.1038/s41586-021-03594-0. Epub 2021 May 10.

Abstract

Betacoronaviruses caused the outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, as well as the current pandemic of SARS coronavirus 2 (SARS-CoV-2)1-4. Vaccines that elicit protective immunity against SARS-CoV-2 and betacoronaviruses that circulate in animals have the potential to prevent future pandemics. Here we show that the immunization of macaques with nanoparticles conjugated with the receptor-binding domain of SARS-CoV-2, and adjuvanted with 3M-052 and alum, elicits cross-neutralizing antibody responses against bat coronaviruses, SARS-CoV and SARS-CoV-2 (including the B.1.1.7, P.1 and B.1.351 variants). Vaccination of macaques with these nanoparticles resulted in a 50% inhibitory reciprocal serum dilution (ID50) neutralization titre of 47,216 (geometric mean) for SARS-CoV-2, as well as in protection against SARS-CoV-2 in the upper and lower respiratory tracts. Nucleoside-modified mRNAs that encode a stabilized transmembrane spike or monomeric receptor-binding domain also induced cross-neutralizing antibody responses against SARS-CoV and bat coronaviruses, albeit at lower titres than achieved with the nanoparticles. These results demonstrate that current mRNA-based vaccines may provide some protection from future outbreaks of zoonotic betacoronaviruses, and provide a multimeric protein platform for the further development of vaccines against multiple (or all) betacoronaviruses.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic
  • Administration, Intranasal
  • Animals
  • Antibodies, Neutralizing / immunology*
  • Betacoronavirus / immunology*
  • COVID-19 / epidemiology
  • COVID-19 / immunology*
  • COVID-19 / prevention & control*
  • COVID-19 Vaccines / immunology
  • Common Cold / immunology
  • Common Cold / prevention & control*
  • Common Cold / virology
  • Cross Reactions / immunology*
  • Disease Models, Animal
  • Female
  • Humans
  • Macaca / immunology
  • Male
  • Models, Molecular
  • Nanoparticles / chemistry
  • Pandemics*
  • SARS-CoV-2 / immunology
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / immunology
  • Trachea
  • Vaccination
  • Viral Vaccines / immunology*

Substances

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

Supplementary concepts

  • SARS-CoV-2 variants