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

• DOI: 10.1128/jvi.79.2.1154-1163.2005
• Publication Date: 2004-12-21T03:05:49Z
• Authors: 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
• Keywords: Antigenicity; V3 loop

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