A trimeric, V2-deleted HIV-1 envelope glycoprotein vaccine elicits potent neutralizing antibodies but limited breadth of neutralization in human volunteers.

Published

Journal Article

BACKGROUND: A key missing element in the development of a successful human immunodeficiency virus (HIV) vaccine is an immunogen that can generate broadly cross-neutralizing antibodies against primary isolates of the virus. METHODS: This phase 1 clinical trial employed a DNA prime and subunit envelope protein boost in an attempt to generate cellular and humoral immune responses that might be desirable in a protective HIV vaccine. Priming was performed via intramuscular injection with gag and env DNA adsorbed to polylactide coglycolide microspheres, followed by boosting with a recombinant trimeric envelope (Env) glycoprotein delivered in MF59 adjuvant. RESULTS: The DNA prime and protein boost were generally safe and well-tolerated. Env-specific CD4(+) cellular responses were generated that were predominantly detected after Env protein boosting. Neutralizing antibody responses against the homologous SF162 viral isolate were remarkably strong and were present in the majority of vaccine recipients, including a strong response against CD4-induced epitopes on gp120. Despite the promising potency of this vaccine approach, neutralization breadth against heterologous tier 2 strains of HIV-1 was minimal. CONCLUSIONS: Potent neutralization against neutralization-sensitive strains of HIV is achievable in humans through a DNA prime, recombinant oligomeric Env protein boost regimen. Eliciting substantial breadth of neutralization remains an elusive goal. CLINICAL TRIALS REGISTRATION: NCT00073216.

Full Text

Duke Authors

Cited Authors

  • Spearman, P; Lally, MA; Elizaga, M; Montefiori, D; Tomaras, GD; McElrath, MJ; Hural, J; De Rosa, SC; Sato, A; Huang, Y; Frey, SE; Sato, P; Donnelly, J; Barnett, S; Corey, LJ; HIV Vaccine Trials Network of NIAID,

Published Date

  • April 15, 2011

Published In

Volume / Issue

  • 203 / 8

Start / End Page

  • 1165 - 1173

PubMed ID

  • 21451004

Pubmed Central ID

  • 21451004

Electronic International Standard Serial Number (EISSN)

  • 1537-6613

Digital Object Identifier (DOI)

  • 10.1093/infdis/jiq175

Language

  • eng

Conference Location

  • United States