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PMID: 15613343 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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

Journal of virology ·Vol. 79 ·No. 2 ·2005-01-00 ·Pages 1154-63

Gao F, Weaver EA, Lu Z, Li Y, Liao HX, Ma B, Alam SM, Scearce RM, Sutherland LL, Yu JS, Decker JM, Shaw GM, Montefiori DC, Korber BT, Hahn BH, Haynes BF

Abstract

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.

MeSH Terms
Amino Acid Sequence Animals Binding Sites CD4 Antigens/metabolism Female Gene Products, env/immunology Genes, env HIV Antibodies/blood HIV Envelope Protein gp120/immunology HIV Envelope Protein gp160/immunology HIV-1/classification,genetics,immunology Humans Mice Mice, Inbred BALB C Molecular Sequence Data Receptors, CCR5/physiology T-Lymphocytes/immunology env Gene Products, Human Immunodeficiency Virus
Chemicals
CD4 Antigens Gene Products, env HIV Antibodies HIV Envelope Protein gp120 HIV Envelope Protein gp160 Receptors, CCR5 env Gene Products, Human Immunodeficiency Virus gp140 envelope protein, Human immunodeficiency virus 1
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Gao Feng
Department of Medicine, Duke University Medical Center, 112 Research Park III, Research Dr., Box 3347, Durham, NC 27710, USA. fgao@duke.edu
Weaver Eric A
Lu Zhongjing
Li Yingying
Liao Hua-Xin
Ma Benjiang
Alam S Munir
Scearce Richard M
Sutherland Laura L
Yu Jae-Sung
Decker Julie M
Shaw George M
Montefiori David C
Korber Bette T
Hahn Beatrice H
Haynes Barton F
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.79.2.1154-1163.2005
Email
fgao@duke.edu
Published
2005-01-00
Pages
1154-63
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC538535
Subset
IM
Grants
NIAID NIH HHS · T32 AI007392 · United States
NIAID NIH HHS · AI55386 · United States
NIAID NIH HHS · P01 AI035351 · United States
NIAID NIH HHS · AI85338 · United States
NIAID NIH HHS · P0-1 AI52816 · United States
NIAID NIH HHS · P30 AI051445 · United States
NIAID NIH HHS · P01 AI052816 · United States
NIAID NIH HHS · R21 AI055386 · United States
NIAID NIH HHS · P0-1 AI51445 · United States
NIAID NIH HHS · U01 AI035351 · United States
NIAID NIH HHS · AI54497 · United States
NIAID NIH HHS · N01AI85338 · United States
NIAID NIH HHS · 5T32 AI07392 · United States
NIAID NIH HHS · AI35351 · United States
External Links
PubMed source DOI: 10.1128/JVI.79.2.1154-1163.2005 PMC Full Text View journal details
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