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

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

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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.

Item Type: Article
Uncontrolled Keywords: HIV-1 genetic variation; Centralized HIV-1 immunogens; HIV-1 envelope glycoprotein; Subtype B
Subjects: MSC 2010, the AMS's Mathematics Subject Classification > 62 Statistics
MSC 2010, the AMS's Mathematics Subject Classification > 92 Biology and other natural sciences
Depositing User: Dr Mark Muldoon
Date Deposited: 31 Jan 2007
Last Modified: 20 Oct 2017 14:12
URI: http://eprints.maths.manchester.ac.uk/id/eprint/697

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