SARS-CoV-2 RBD trimer protein adjuvanted with Alum-3M-052 protects from SARS-CoV-2 infection and immune pathology in the lung

Nat Commun. 2021 Jun 11;12(1):3587. doi: 10.1038/s41467-021-23942-y.

Abstract

There is a great need for the development of vaccines that induce potent and long-lasting protective immunity against SARS-CoV-2. Multimeric display of the antigen combined with potent adjuvant can enhance the potency and longevity of the antibody response. The receptor binding domain (RBD) of the spike protein is a primary target of neutralizing antibodies. Here, we developed a trimeric form of the RBD and show that it induces a potent neutralizing antibody response against live virus with diverse effector functions and provides protection against SARS-CoV-2 challenge in mice and rhesus macaques. The trimeric form induces higher neutralizing antibody titer compared to monomer with as low as 1μg antigen dose. In mice, adjuvanting the protein with a TLR7/8 agonist formulation alum-3M-052 induces 100-fold higher neutralizing antibody titer and superior protection from infection compared to alum. SARS-CoV-2 infection causes significant loss of innate cells and pathology in the lung, and vaccination protects from changes in innate cells and lung pathology. These results demonstrate RBD trimer protein as a suitable candidate for vaccine against SARS-CoV-2.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Alum Compounds / administration & dosage
  • Angiotensin-Converting Enzyme 2 / immunology
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Antibody Formation / immunology
  • COVID-19 / immunology*
  • COVID-19 / prevention & control*
  • COVID-19 Vaccines / administration & dosage
  • COVID-19 Vaccines / immunology*
  • Disease Models, Animal
  • Heterocyclic Compounds, 3-Ring / administration & dosage*
  • Heterocyclic Compounds, 3-Ring / immunology
  • Humans
  • Macaca mulatta
  • Mice
  • Protein Binding
  • SARS-CoV-2 / isolation & purification
  • Spike Glycoprotein, Coronavirus / immunology
  • Stearic Acids / administration & dosage*
  • Stearic Acids / immunology

Substances

  • Adjuvants, Immunologic
  • Alum Compounds
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Heterocyclic Compounds, 3-Ring
  • Spike Glycoprotein, Coronavirus
  • Stearic Acids
  • spike protein, SARS-CoV-2
  • MEDI9197
  • aluminum sulfate
  • Angiotensin-Converting Enzyme 2