Tracing HIV-1 strains that imprint broadly neutralizing antibody responses

Nature. 2018 Sep;561(7723):406-410. doi: 10.1038/s41586-018-0517-0. Epub 2018 Sep 10.

Abstract

Understanding the determinants of broadly neutralizing antibody (bNAb) evolution is crucial for the development of bNAb-based HIV vaccines1. Despite emerging information on cofactors that promote bNAb evolution in natural HIV-1 infections, in which the induction of bNAbs is genuinely rare2, information on the impact of the infecting virus strain on determining the breadth and specificity of the antibody responses to HIV-1 is lacking. Here we analyse the influence of viral antigens in shaping antibody responses in humans. We call the ability of a virus strain to induce similar antibody responses across different hosts its antibody-imprinting capacity, which from an evolutionary biology perspective corresponds to the viral heritability of the antibody responses. Analysis of 53 measured parameters of HIV-1-binding and neutralizing antibody responses in a cohort of 303 HIV-1 transmission pairs (individuals who harboured highly related HIV-1 strains and were putative direct transmission partners or members of an HIV-1 transmission chain) revealed that the effect of the infecting virus on the outcome of the bNAb response is moderate in magnitude but highly significant. We introduce the concept of bNAb-imprinting viruses and provide evidence for the existence of such viruses in a systematic screening of our cohort. The bNAb-imprinting capacity can be substantial, as indicated by a transmission pair with highly similar HIV-1 antibody responses and strong bNAb activity. Identification of viruses that have bNAb-imprinting capacities and their characterization may thus provide the potential to develop lead immunogens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / immunology
  • Antibodies, Neutralizing / analysis
  • Antibodies, Neutralizing / immunology*
  • Female
  • HIV Antibodies / analysis
  • HIV Antibodies / immunology*
  • HIV Infections / immunology*
  • HIV Infections / transmission
  • HIV Infections / virology*
  • HIV-1 / classification*
  • HIV-1 / immunology*
  • HIV-1 / isolation & purification
  • Humans
  • Male

Substances

  • AIDS Vaccines
  • Antibodies, Neutralizing
  • HIV Antibodies