Coping with Viral Diversity in HIV Vaccine Design

The ability of human immunodeficiency virus type 1 (HIV-1) to develop high levels of genetic diversity, and thereby acquire mutations to escape immune pressures, contributes to the difficulties in producing a vaccine. Possibly no single HIV-1 sequence can induce sufficiently broad immunity to protec...

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Main Authors:	Nickle, David C, Rolland, Morgane, Jensen, Mark A, Pond, Sergei L. Kosakovsky, Deng, Wenjie, Seligman, Mark, Heckerman, David, Mullins, James I, Jojic, Nebojsa
Format:	Online
Language:	English
Published:	Public Library of Science 2007
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1857809/

id	pubmed-1857809
recordtype	oai_dc
spelling	pubmed-18578092007-04-28 Coping with Viral Diversity in HIV Vaccine Design Nickle, David C Rolland, Morgane Jensen, Mark A Pond, Sergei L. Kosakovsky Deng, Wenjie Seligman, Mark Heckerman, David Mullins, James I Jojic, Nebojsa Research Article The ability of human immunodeficiency virus type 1 (HIV-1) to develop high levels of genetic diversity, and thereby acquire mutations to escape immune pressures, contributes to the difficulties in producing a vaccine. Possibly no single HIV-1 sequence can induce sufficiently broad immunity to protect against a wide variety of infectious strains, or block mutational escape pathways available to the virus after infection. The authors describe the generation of HIV-1 immunogens that minimizes the phylogenetic distance of viral strains throughout the known viral population (the center of tree [COT]) and then extend the COT immunogen by addition of a composite sequence that includes high-frequency variable sites preserved in their native contexts. The resulting COT+ antigens compress the variation found in many independent HIV-1 isolates into lengths suitable for vaccine immunogens. It is possible to capture 62% of the variation found in the Nef protein and 82% of the variation in the Gag protein into immunogens of three gene lengths. The authors put forward immunogen designs that maximize representation of the diverse antigenic features present in a spectrum of HIV-1 strains. These immunogens should elicit immune responses against high-frequency viral strains as well as against most mutant forms of the virus. Public Library of Science 2007-04 2007-04-27 /pmc/articles/PMC1857809/ /pubmed/17465674 http://dx.doi.org/10.1371/journal.pcbi.0030075 Text en © 2007 Nickle et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Nickle, David C Rolland, Morgane Jensen, Mark A Pond, Sergei L. Kosakovsky Deng, Wenjie Seligman, Mark Heckerman, David Mullins, James I Jojic, Nebojsa
spellingShingle	Nickle, David C Rolland, Morgane Jensen, Mark A Pond, Sergei L. Kosakovsky Deng, Wenjie Seligman, Mark Heckerman, David Mullins, James I Jojic, Nebojsa Coping with Viral Diversity in HIV Vaccine Design
author_facet	Nickle, David C Rolland, Morgane Jensen, Mark A Pond, Sergei L. Kosakovsky Deng, Wenjie Seligman, Mark Heckerman, David Mullins, James I Jojic, Nebojsa
author_sort	Nickle, David C
title	Coping with Viral Diversity in HIV Vaccine Design
title_short	Coping with Viral Diversity in HIV Vaccine Design
title_full	Coping with Viral Diversity in HIV Vaccine Design
title_fullStr	Coping with Viral Diversity in HIV Vaccine Design
title_full_unstemmed	Coping with Viral Diversity in HIV Vaccine Design
title_sort	coping with viral diversity in hiv vaccine design
description	The ability of human immunodeficiency virus type 1 (HIV-1) to develop high levels of genetic diversity, and thereby acquire mutations to escape immune pressures, contributes to the difficulties in producing a vaccine. Possibly no single HIV-1 sequence can induce sufficiently broad immunity to protect against a wide variety of infectious strains, or block mutational escape pathways available to the virus after infection. The authors describe the generation of HIV-1 immunogens that minimizes the phylogenetic distance of viral strains throughout the known viral population (the center of tree [COT]) and then extend the COT immunogen by addition of a composite sequence that includes high-frequency variable sites preserved in their native contexts. The resulting COT+ antigens compress the variation found in many independent HIV-1 isolates into lengths suitable for vaccine immunogens. It is possible to capture 62% of the variation found in the Nef protein and 82% of the variation in the Gag protein into immunogens of three gene lengths. The authors put forward immunogen designs that maximize representation of the diverse antigenic features present in a spectrum of HIV-1 strains. These immunogens should elicit immune responses against high-frequency viral strains as well as against most mutant forms of the virus.
publisher	Public Library of Science
publishDate	2007
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1857809/
_version_	1611395990057648128

Coping with Viral Diversity in HIV Vaccine Design

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