Virus vaccines: proteins prefer prolines

Cell Host Microbe. 2021 Mar 10;29(3):327-333. doi: 10.1016/j.chom.2021.02.002.

Abstract

Most viral vaccines are based on inducing neutralizing antibodies (NAbs) against the virus envelope or spike glycoproteins. Many viral surface proteins exist as trimers that transition from a pre-fusion state when key NAb epitopes are exposed to a post-fusion form in which the potential for virus-cell fusion no longer exists. For optimal vaccine performance, these viral proteins are often engineered to enhance stability and presentation of these NAb epitopes. The method involves the structure-guided introduction of proline residues at key positions that maintain the trimer in the pre-fusion configuration. We review how this technique emerged during HIV-1 Env vaccine development and its subsequent wider application to other viral vaccines including SARS-CoV-2.

Keywords: COVID-19; Ebola; HIV-1; Lassa; MERS; RSV; SARS; SARS-CoV-2; envelope; glycoprotein; hMPV; protein engineering; spike; vaccine; virus.

Publication types

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

MeSH terms

  • Antibodies, Neutralizing / immunology
  • COVID-19 Vaccines / chemistry
  • COVID-19 Vaccines / genetics
  • COVID-19 Vaccines / immunology
  • Humans
  • Models, Molecular
  • Proline / chemistry*
  • Proline / genetics
  • Proline / immunology*
  • Protein Engineering
  • Viral Vaccines / chemistry*
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology*

Substances

  • Antibodies, Neutralizing
  • COVID-19 Vaccines
  • Viral Vaccines
  • Proline