Overcoming Steric Restrictions of VRC01 HIV-1 Neutralizing Antibodies through Immunization.

Journal Article (Journal Article)

Broadly HIV-1 neutralizing VRC01 class antibodies target the CD4-binding site of Env. They are derived from VH1-2∗02 antibody heavy chains paired with rare light chains expressing 5-amino acid-long CDRL3s. They have been isolated from infected subjects but have not yet been elicited by immunization. Env-derived immunogens capable of binding the germline forms of VRC01 B cell receptors on naive B cells have been designed and evaluated in knockin mice. However, the elicited antibodies cannot bypass glycans present on the conserved position N276 of Env, which restricts access to the CD4-binding site. Efforts to guide the appropriate maturation of these antibodies by sequential immunization have not yet been successful. Here, we report on a two-step immunization scheme that leads to the maturation of VRC01-like antibodies capable of accommodating the N276 glycan and displaying autologous tier 2 neutralizing activities. Our results are relevant to clinical trials aiming to elicit VRC01 antibodies.

Full Text

Duke Authors

Cited Authors

  • Parks, KR; MacCamy, AJ; Trichka, J; Gray, M; Weidle, C; Borst, AJ; Khechaduri, A; Takushi, B; Agrawal, P; Guenaga, J; Wyatt, RT; Coler, R; Seaman, M; LaBranche, C; Montefiori, DC; Veesler, D; Pancera, M; McGuire, A; Stamatatos, L

Published Date

  • December 3, 2019

Published In

Volume / Issue

  • 29 / 10

Start / End Page

  • 3060 - 3072.e7

PubMed ID

  • 31801073

Pubmed Central ID

  • PMC6936959

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2019.10.071

Language

  • eng

Conference Location

  • United States