Antigenicity and immunogenicity of a synthetic human immunodeficiency virus type 1 group m consensus envelope glycoprotein.

Published

Journal Article

Genetic variation of human immunodeficiency virus (HIV-1) represents a major obstacle for AIDS vaccine development. To decrease the genetic distances between candidate immunogens and field virus strains, we have designed and synthesized an artificial group M consensus env gene (CON6 gene) to be equidistant from contemporary HIV-1 subtypes and recombinants. This novel envelope gene expresses a glycoprotein that binds soluble CD4, utilizes CCR5 but not CXCR4 as a coreceptor, and mediates HIV-1 entry. Key linear, conformational, and glycan-dependent monoclonal antibody epitopes are preserved in CON6, and the glycoprotein is recognized equally well by sera from individuals infected with different HIV-1 subtypes. When used as a DNA vaccine followed by a recombinant vaccinia virus boost in BALB/c mice, CON6 env gp120 and gp140CF elicited gamma interferon-producing T-cell responses that recognized epitopes within overlapping peptide pools from three HIV-1 Env proteins, CON6, MN (subtype B), and Chn19 (subtype C). Sera from guinea pigs immunized with recombinant CON6 Env gp120 and gp140CF glycoproteins weakly neutralized selected HIV-1 primary isolates. Thus, the computer-generated "consensus" env genes are capable of expressing envelope glycoproteins that retain the structural, functional, and immunogenic properties of wild-type HIV-1 envelopes.

Full Text

Duke Authors

Cited Authors

  • Gao, F; Weaver, EA; Lu, Z; Li, Y; Liao, H-X; Ma, B; Alam, SM; Scearce, RM; Sutherland, LL; Yu, J-S; Decker, JM; Shaw, GM; Montefiori, DC; Korber, BT; Hahn, BH; Haynes, BF

Published Date

  • January 2005

Published In

Volume / Issue

  • 79 / 2

Start / End Page

  • 1154 - 1163

PubMed ID

  • 15613343

Pubmed Central ID

  • 15613343

Electronic International Standard Serial Number (EISSN)

  • 1098-5514

International Standard Serial Number (ISSN)

  • 0022-538X

Digital Object Identifier (DOI)

  • 10.1128/jvi.79.2.1154-1163.2005

Language

  • eng