Antigenicity and Immunogenicity of Transmitted/Founder, Consensus, and Chronic Envelope Glycoproteins of Human Immunodeficiency Virus Type 1

Liao, Hua-Xin and Tsao, Chun-Yen and Alam, S. Munir and Muldoon, Mark and Vandergrift, Nathan and Ma, Ben-Jiang and Lu, Xiaozhi and Sutherland, Laura L and Scearce, Richard M. and Bowman, Cindy and Parks, Robert and Chen, Haiyan and Blinn, Julie H and Lapedes, Alan and Watson, Sydeaka and Xia, Shi-Mao and Foulger, Andrew and Hahn, Beatrice H and Shaw, George M and Swanstrom, Ron and Montefiori, David C and Gao, Feng and Haynes, Barton F and Korber, Bette (2013) Antigenicity and Immunogenicity of Transmitted/Founder, Consensus, and Chronic Envelope Glycoproteins of Human Immunodeficiency Virus Type 1. Journal of Virology, 87 (8). pp. 4185-4201. ISSN 0022-538X

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Abstract

Human immunodeficiency virus type 1 (HIV-1) vaccine development requires selection of appropriate envelope (Env) immunogens. Twenty HIV-1 Env glycoproteins were examined for their ability to bind human anti-HIV-1 monoclonal antibodies (MAbs) and then used as immunogens in guinea pigs to identify promising immunogens. These included five Envs derived from chronically infected individuals, each representing one of five common clades and eight consensus Envs based on these five clades, as well as the consensus of the entire HIV-1 M group, and seven transmitted/founder (T/F) Envs from clades B and C. Sera from immunized guinea pigs were tested for neutralizing activity using 36 HIV-1 Env-pseudotyped viruses. All Envs bound to CD4 binding site, membrane-proximal, and V1/V2 MAbs with similar apparent affinities, although the T/F Envs bound with higher affinity to the MAb 17b, a CCR5 coreceptor binding site antibody. However, the various Envs differed in their ability to induce neutralizing antibodies. Consensus Envs elicited the most potent responses, but neutralized only a subset of viruses, including mostly easy-to-neutralize tier 1 and some more-difficult-to-neutralize tier 2 viruses. T/F Envs elicited fewer potent neutralizing antibodies but exhibited greater breadth than chronic or consensus Envs. Finally, chronic Envs elicited the lowest level and most limited breadth of neutralizing antibodies overall. Thus, each group of Env immunogens elicited a different antibody response profile. The complementary benefits of consensus and T/F Env immunogens raise the possibility that vaccines utilizing a combination of consensus and T/F Envs may be able to induce neutralizing responses with greater breadth and potency than single Env immunogens.

Item Type: Article
Uncontrolled Keywords: HIV envelope protein, HIV-1 vaccine, neutralising antibodies
Subjects: MSC 2010, the AMS's Mathematics Subject Classification > 92 Biology and other natural sciences
Depositing User: Dr Mark Muldoon
Date Deposited: 15 May 2013
Last Modified: 20 Oct 2017 14:13
URI: http://eprints.maths.manchester.ac.uk/id/eprint/1978

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