Discovery medicine - the HVTN's iterative approach to developing an HIV-1 broadly neutralizing vaccine

Curr Opin HIV AIDS. 2023 Nov 1;18(6):290-299. doi: 10.1097/COH.0000000000000821. Epub 2023 Sep 13.

Abstract

Purpose of review: In the past two decades, there has been an explosion in the discovery of HIV-1 broadly neutralizing antibodies (bnAbs) and associated vaccine strategies to induce them. This abundance of approaches necessitates a system that accurately and expeditiously identifies the most promising regimens. We herein briefly review the background science of bnAbs, provide a description of the first round of phase 1 discovery medicine studies, and suggest an approach to integrate these into a comprehensive HIV-1-neutralizing vaccine.

Recent findings: With recent preclinical success including induction of early stage bnAbs in mouse knockin models and rhesus macaques, successful priming of VRC01-class bnAbs with eOD-GT8 in a recent study in humans, and proof-of-concept that intravenous infusion of VRC01 prevents sexual transmission of virus in humans, the stage is set for a broad and comprehensive bnAb vaccine program. Leveraging significant advances in protein nanoparticle science, mRNA technology, adjuvant development, and B-cell and antibody analyses, the HVTN has reconfigured its HIV-1 vaccine strategy by developing the Discovery Medicine Program to test promising vaccine candidates targeting six key epitopes.

Summary: The HVTN Discovery Medicine program is testing multiple HIV-1-neutralizing vaccine candidates.

Publication types

  • Review

MeSH terms

  • AIDS Vaccines* / administration & dosage
  • AIDS Vaccines* / genetics
  • AIDS Vaccines* / immunology
  • Animals
  • Antibodies, Neutralizing / immunology
  • Broadly Neutralizing Antibodies / immunology
  • HIV Antibodies* / immunology
  • HIV Infections* / immunology
  • HIV Infections* / prevention & control
  • HIV-1* / genetics
  • HIV-1* / immunology
  • Humans
  • Macaca mulatta
  • Mice
  • Vaccine Development / methods

Substances

  • AIDS Vaccines
  • HIV Antibodies
  • Antibodies, Neutralizing
  • Broadly Neutralizing Antibodies