Analysis of HIV-1 subtype B third variable region peptide motifs for induction of neutralizing antibodies against HIV-1 primary isolates |
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Authors: | Haynes Barton F Ma Benjiang Montefiori David C Wrin Terri Petropoulos Christos J Sutherland Laura L Scearce Richard M Denton Cathrine Xia Shi-Mao Korber Bette T Liao Hua-Xin |
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Institution: | Department of Medicine and Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA. hayne002@mc.duke.edu |
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Abstract: | The HIV-1 gp120 V3 loop is a potent inducer of neutralizing antibodies for T cell line adapted-HIV-1, but less so for primary isolates. We hypothesized that peptides representative of the diversity of natural HIV-1 V3 loop variants might capture elements of conserved higher order structures and so stimulate broadly reactive neutralizing antibodies. We designed a panel of 29 subtype B V3 sequences postulated to reflect the range of V3 diversity. These peptides were used to immunize guinea pigs. The most effective peptide (62.19) clustered around the subtype B consensus sequence and induced antibodies that reproducibly neutralized 31% of the subtype B HIV-1 primary isolates evaluated, but exhibited limited cross-neutralization of non-subtype B HIV-1 strains. Taken together, these data demonstrated that the limited neutralization profile of antibodies induced by optimal subtype B V3 motifs likely represents the maximum breadth of neutralization of subtype B HIV-1 primary isolates attainable by anti-V3 peptide antibodies. |
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Keywords: | HIV-1 vaccine HIV-1 envelope V3 loop Neutralization Antibody Peptide Immunogen Guinea pig |
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