2007.11: Antigenicity and immunogenicity of HIV-1 consensus subtype B envelope glycoproteins

2007.11: Denise L. Kothe, Julie M. Decker, Yingying Li, Zhiping Weng, Frederic Bibollet-Ruche, Kenneth P. Zammit, Maraia G. Slazar, Yalu Chen, Jesus F. Salazar-Gonzalez, Zina Moldoveanu, Jiri Mestecky, Feng Gao, Barton F. Haynes, George M. Shaw, Mark Muldoon, Bette T. M. Korber and Beatrice H. Hahn (2007) Antigenicity and immunogenicity of HIV-1 consensus subtype B envelope glycoproteins. Virology, 360 (1). pp. 218-234. ISSN 0042-6822

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DOI: 10.1016/j.virol.2006.10.017

Abstract

“Centralized” (ancestral and consensus) HIV-1 envelope immunogens induce broadly cross-reactive T cell responses in laboratory animals; however, their potential to elicit cross-reactive neutralizing antibodies has not been fully explored. Here, we report the construction of a panel of consensus subtype B (ConB) envelopes and compare their biologic, antigenic, and immunogenic properties to those of two wild-type Env controls from individuals with early and acute HIV-1 infection. Glycoprotein expressed from full-length (gp160), uncleaved (gp160-UNC), truncated (gp145), and N-linked glycosylation site deleted (gp160-201N/S) versions of the ConB env gene were packaged into virions and, except for the fusion defective gp160-UNC, mediated infection via the CCR5 co-receptor. Pseudovirions containing ConB Envs were sensitive to neutralization by patient plasma and monoclonal antibodies, indicating the preservation of neutralizing epitopes found in contemporary subtype B viruses. When used as DNA vaccines in guinea pigs, ConB and wild-type env immunogens induced appreciable binding, but overall only low level neutralizing antibodies. However, all four ConB immunogens were significantly more potent than one wild-type vaccine at eliciting neutralizing antibodies against a panel of tier 1 and tier 2 viruses, and ConB gp145 and gp160 were significantly more potent than both wild-type vaccines at inducing neutralizing antibodies against tier 1 viruses. Thus, consensus subtype B env immunogens appear to be at least as good as, and in some instances better than, wild-type B env immunogens at inducing a neutralizing antibody response, and are amenable to further improvement by specific gene modifications.

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