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Increased sequence coverage through combined targeting of variant and conserved epitopes correlates with control of HIV replication.

ABSTRACT: A major challenge in the development of an HIV vaccine is that of contending with the extensive sequence variability found in circulating viruses. Induction of HIV-specific T-cell responses targeting conserved regions and induction of HIV-specific T-cell responses recognizing a high number of epitope variants have both been proposed as strategies to overcome this challenge. We addressed the ability of cytotoxic T lymphocytes from 30 untreated HIV-infected subjects with and without control of virus replication to recognize all clade B Gag sequence variants encoded by at least 5% of the sequences in the Los Alamos National Laboratory HIV database (1,300 peptides) using gamma interferon and interleukin-2 (IFN-?/IL-2) FluoroSpot analysis. While targeting of conserved regions was similar in the two groups (P = 0.47), we found that subjects with control of virus replication demonstrated marginally lower recognition of Gag epitope variants than subjects with normal progression (P = 0.05). In viremic controllers and progressors, we found variant recognition to be associated with viral load (r = 0.62, P = 0.001). Interestingly, we show that increased overall sequence coverage, defined as the overall proportion of HIV database sequences targeted through the Gag-specific repertoire, is inversely associated with viral load (r = -0.38, P = 0.03). Furthermore, we found that sequence coverage, but not variant recognition, correlated with increased recognition of a panel of clade B HIV founder viruses (r = 0.50, P = 0.004). We propose sequence coverage by HIV Gag-specific immune responses as a possible correlate of protection that may contribute to control of virus replication. Additionally, sequence coverage serves as a valuable measure by which to evaluate the protective potential of future vaccination strategies.

SUBMITTER: Sunshine J

PROVIDER: S-EPMC3911649 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Increased sequence coverage through combined targeting of variant and conserved epitopes correlates with control of HIV replication.

Sunshine Justine J Kim Moon M Carlson Jonathan M JM Heckerman David D Czartoski Julie J Migueles Stephen A SA Maenza Janine J McElrath M Juliana MJ Mullins James I JI Frahm Nicole N

Journal of virology 20131113 2

A major challenge in the development of an HIV vaccine is that of contending with the extensive sequence variability found in circulating viruses. Induction of HIV-specific T-cell responses targeting conserved regions and induction of HIV-specific T-cell responses recognizing a high number of epitope variants have both been proposed as strategies to overcome this challenge. We addressed the ability of cytotoxic T lymphocytes from 30 untreated HIV-infected subjects with and without control of vir ...[more]

PMID: 24227851

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Increased sequence coverage through combined targeting of variant and conserved epitopes correlates with control of HIV replication.

Publications

Increased sequence coverage through combined targeting of variant and conserved epitopes correlates with control of HIV replication.

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