A class II MHC-targeted vaccine elicits immunity against SARS-CoV-2 and its variants

Proc Natl Acad Sci U S A. 2021 Nov 2;118(44):e2116147118. doi: 10.1073/pnas.2116147118.

Abstract

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in over 100 million infections and millions of deaths. Effective vaccines remain the best hope of curtailing SARS-CoV-2 transmission, morbidity, and mortality. The vaccines in current use require cold storage and sophisticated manufacturing capacity, which complicates their distribution, especially in less developed countries. We report the development of a candidate SARS-CoV-2 vaccine that is purely protein based and directly targets antigen-presenting cells. It consists of the SARS-CoV-2 Spike receptor-binding domain (SpikeRBD) fused to an alpaca-derived nanobody that recognizes class II major histocompatibility complex antigens (VHHMHCII). This vaccine elicits robust humoral and cellular immunity against SARS-CoV-2 and its variants. Both young and aged mice immunized with two doses of VHHMHCII-SpikeRBD elicit high-titer binding and neutralizing antibodies. Immunization also induces strong cellular immunity, including a robust CD8 T cell response. VHHMHCII-SpikeRBD is stable for at least 7 d at room temperature and can be lyophilized without loss of efficacy.

Keywords: COVID-19; nanobody; vaccine.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Neutralizing / biosynthesis
  • Antibodies, Viral / biosynthesis
  • Antigen-Presenting Cells / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • COVID-19 / epidemiology
  • COVID-19 / immunology*
  • COVID-19 / prevention & control*
  • COVID-19 Vaccines / administration & dosage
  • COVID-19 Vaccines / immunology*
  • COVID-19 Vaccines / pharmacology*
  • Camelids, New World / immunology
  • Female
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Immunity, Cellular
  • Immunity, Humoral
  • Immunization, Secondary
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Pandemics* / prevention & control
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / immunology*
  • Single-Domain Antibodies / administration & dosage
  • Single-Domain Antibodies / immunology
  • Spike Glycoprotein, Coronavirus / administration & dosage
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Histocompatibility Antigens Class II
  • Recombinant Fusion Proteins
  • Single-Domain Antibodies
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2