The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies

J Virol. 2023 Nov 30;97(11):e0141423. doi: 10.1128/jvi.01414-23. Epub 2023 Nov 9.

Abstract

The wide endemic range of mosquito-vectored flaviviruses-such as Zika virus and dengue virus serotypes 1-4-places hundreds of millions of people at risk of infection every year. Despite this, there are no widely available vaccines, and treatment of severe cases is limited to supportive care. An avenue toward development of more widely applicable vaccines and targeted therapies is the characterization of monoclonal antibodies that broadly neutralize all these viruses. Here, we measure how single amino acid mutations in viral envelope protein affect neutralizing antibodies with both broad and narrow specificities. We find that broadly neutralizing antibodies with potential as vaccine prototypes or biological therapeutics are quantifiably more difficult to escape than narrow, virus-specific neutralizing antibodies.

Keywords: Zika; broadly neutralizing antibodies; deep mutational scanning; dengue.

MeSH terms

  • Animals
  • Antibodies, Viral*
  • Broadly Neutralizing Antibodies*
  • Cross Reactions
  • Humans
  • Mutation
  • Vaccines
  • Viral Envelope
  • Viral Envelope Proteins* / genetics
  • Zika Virus Infection* / immunology
  • Zika Virus Infection* / therapy
  • Zika Virus* / genetics

Substances

  • Antibodies, Viral
  • Broadly Neutralizing Antibodies
  • Vaccines
  • Viral Envelope Proteins