Antigenicity and immunogenicity of a synthetic human immunodeficiency virus type 1 group m consensus envelope glycoprotein.
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.
Gao
Feng
F
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
EA
Lu
Zhongjing
Z
Li
Yingying
Y
Liao
Hua-Xin
HX
Ma
Benjiang
B
Alam
S Munir
SM
Scearce
Richard M
RM
Sutherland
Laura L
LL
Yu
Jae-Sung
JS
Decker
Julie M
JM
Shaw
George M
GM
Montefiori
David C
DC
Korber
Bette T
BT
Hahn
Beatrice H
BH
Haynes
Barton F
BF
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism; D005260:Female; D015686:Gene Products, env / Q000276:immunology*; D015752:Genes, env; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D019302:HIV Envelope Protein gp160 / Q000276:immunology; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D019713:Receptors, CCR5 / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus
D015704:CD4 Antigens; D015686:Gene Products, env; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D019713:Receptors, CCR5; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1