Antigenicity and Immunogenicity of a Synthetic Human Immunodeficiency Virus Type 1 Group M Consensus Envelope Glycoprotein

Authors

Feng Gao, Duke University Medical Center, DurhamFollow
Eric A. Weaver, Duke University Medical Center, Durham & University of Nebraska-LincolnFollow
Zhongjing Lu, uke University Medical Center, Durham
Yingying Li, University of Alabama at Birmingham
Hua-Xin Liao, Duke University Medical Center, Durham
Benjiang Ma, Duke University Medical Center, Durham
S. Munir Alam, Duke University Medical Center, Durham
Richard M. Scearce, uke University MedicalDuke University Medical Center, Durham Center, Durham
Laura L. Sutherland, Duke University Medical Center, Durham
Jae-Sung Yu, Duke University Medical Center, Durham
Julie M. Decker, Howard Hughes Medical Institute
George M. Shaw, Howard Hughes Medical Institute
David C. Montefiori, Duke University Medical Center, Durham
Bette T. Korber, Los Alamos National Laboratory, Los Alamo
Beatrice H. Hahn, University of Alabama at Birmingham
Barton F. Haynes, Duke University Medical CenterFollow

Document Type

Article

Date of this Version

2005

Citation

JOURNAL OF VIROLOGY, Jan. 2005, p. 1154–1163 Vol. 79, No. 2

doi:10.1128/JVI.79.2.1154–1163.2005

Comments

2005, American Society for Microbiology. All Rights Reserved.

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.