Modifications of the human immunodeficiency virus envelope glycoprotein enhance immunogenicity for genetic immunization.

Published

Journal Article

In this study, we have investigated the effect of specific mutations in human immunodeficiency virus type 1 (HIV-1) envelope (Env) on antibody production in an effort to improve humoral immune responses to this glycoprotein by DNA vaccination. Mice were injected with plasmid expression vectors encoding HIV Env with modifications in regions that might affect this response. Elimination of conserved glycosylation sites did not substantially enhance humoral or cytotoxic-T-lymphocyte (CTL) immunity. In contrast, a modified gp140 with different COOH-terminal mutations intended to mimic a fusion intermediate and stabilize trimer formation enhanced humoral immunity without reducing the efficacy of the CTL response. This mutant, with deletions in the cleavage site, fusogenic domain, and spacing of heptad repeats 1 and 2, retained native antigenic conformational determinants as defined by binding to known monoclonal antibodies or CD4, oligomer formation, and virus neutralization in vitro. Importantly, this modified Env, gp140 Delta CFI, stimulated the antibody response to native gp160 while it retained its ability to induce a CTL response, a desirable feature for an AIDS vaccine.

Full Text

Duke Authors

Cited Authors

  • Chakrabarti, BK; Kong, W-P; Wu, B-Y; Yang, Z-Y; Friborg, J; Ling, X; King, SR; Montefiori, DC; Nabel, GJ

Published Date

  • June 2002

Published In

Volume / Issue

  • 76 / 11

Start / End Page

  • 5357 - 5368

PubMed ID

  • 11991964

Pubmed Central ID

  • 11991964

International Standard Serial Number (ISSN)

  • 0022-538X

Digital Object Identifier (DOI)

  • 10.1128/jvi.76.11.5357-5368.2002

Language

  • eng

Conference Location

  • United States