Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site.

Published

Journal Article

Antibodies that neutralize autologous transmitted/founder (TF) HIV occur in most HIV-infected individuals and can evolve to neutralization breadth. Autologous neutralizing antibodies (nAbs) against neutralization-resistant (Tier-2) viruses are rarely induced by vaccination. Whereas broadly neutralizing antibody (bnAb)-HIV-Envelope structures have been defined, the structures of autologous nAbs have not. Here, we show that immunization with TF mutant Envs gp140 oligomers induced high-titer, V5-dependent plasma neutralization for a Tier-2 autologous TF evolved mutant virus. Structural analysis of autologous nAb DH427 revealed binding to V5, demonstrating the source of narrow nAb specificity and explaining the failure to acquire breadth. Thus, oligomeric TF Envs can elicit autologous nAbs to Tier-2 HIVs, but induction of bnAbs will require targeting of precursors of B cell lineages that can mature to heterologous neutralization.

Full Text

Duke Authors

Cited Authors

  • Bradley, T; Fera, D; Bhiman, J; Eslamizar, L; Lu, X; Anasti, K; Zhang, R; Sutherland, LL; Scearce, RM; Bowman, CM; Stolarchuk, C; Lloyd, KE; Parks, R; Eaton, A; Foulger, A; Nie, X; Karim, SSA; Barnett, S; Kelsoe, G; Kepler, TB; Alam, SM; Montefiori, DC; Moody, MA; Liao, H-X; Morris, L; Santra, S; Harrison, SC; Haynes, BF

Published Date

  • January 2016

Published In

Volume / Issue

  • 14 / 1

Start / End Page

  • 43 - 54

PubMed ID

  • 26725118

Pubmed Central ID

  • 26725118

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

International Standard Serial Number (ISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2015.12.017

Language

  • eng