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Coping with viral diversity in HIV vaccine design
Nickle, DC Rolland, M Jensen, MA Kosakovsky Pond, SL Deng, W Seligman, M Heckerman, D Mullins, JI Jojic, N
Nickle, DC
Rolland, M
Jensen, MA
Kosakovsky Pond, SL
Deng, W
Seligman, M
Heckerman, D
Mullins, JI
Jojic, N
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Journal Article
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2007-04-01
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10.1371/journal.pcbi.0030075
Abstract
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 highfrequency 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. © 2007 Nickle et al.
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PLoS Computational Biology
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