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

Feng Gao, Eric A. Weaver, Zhongjing Lu, Yingying Li, Hua Xin Liao, Benjiang Ma, S. Munir Alam, Richard M. Scearce, Laura L. Sutherland, Jae Sung Yu, Julie M. Decker, George M. Shaw, David C. Montefiori, Bette T. Korber, Beatrice H. Hahn, Barton F. Haynes

Research output: Contribution to journalArticle

165 Scopus citations

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 giycoprotein 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 pep tide 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.

Original languageEnglish (US)
Pages (from-to)1154-1163
Number of pages10
JournalJournal of virology
Volume79
Issue number2
DOIs
StatePublished - Jan 1 2005

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Gao, F., Weaver, E. A., Lu, Z., Li, Y., Liao, H. X., Ma, B., Alam, S. M., Scearce, R. M., Sutherland, L. L., Yu, J. S., Decker, J. M., Shaw, G. M., Montefiori, D. C., Korber, B. T., Hahn, B. H., & Haynes, B. F. (2005). Antigenicity and immunogenicity of a synthetic human immunodeficiency virus type 1 group M consensus envelope glycoprotein. Journal of virology, 79(2), 1154-1163. https://doi.org/10.1128/JVI.79.2.1154-1163.2005