4.6 Review

Native-like Env trimers as a platform for HIV-1 vaccine design

Journal

IMMUNOLOGICAL REVIEWS
Volume 275, Issue 1, Pages 161-182

Publisher

WILEY
DOI: 10.1111/imr.12481

Keywords

Env trimers; HIV-1 vaccines; neutralizing antibodies

Categories

Funding

  1. NIH [P01 AI110657]
  2. Collaboration for AIDS Vaccine Discovery (CAVD) grants from the Bill and Melinda Gates Foundation [OPP1111923, OPP1132237]
  3. European Union's Horizon research and innovation programme [681137]
  4. Aids Fonds Netherlands [2011032, 2012041, 2016019]
  5. Vidi grant from the Netherlands Organization for Scientific Research [917.11.314]
  6. Starting Investigator Grant from the European Research Council [ERC-StG-2011-280829-SHEV]

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We describe the development and potential use of various designs of recombinant HIV-1 envelope glycoprotein trimers that mimic the structure of the virion-associated spike, which is the target for neutralizing antibodies. The goal of trimer development programs is to induce broadly neutralizing antibodies with the potential to intervene against multiple circulating HIV-1 strains. Among the topics we address are the designs of various constructs; how native-like trimers can be produced and purified; the properties of such trimers in vitro and their immunogenicity in various animals; and the immunization strategies that may lead to the eventual elicitation of broadly neutralizing antibodies. In summary, native-like trimers are a now a platform for structure- and immunology-based design improvements that could eventually yield immunogens of practical value for solving the long-standing HIV-1 vaccine problem.

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