Cross-clade recognition and neutralization by the V3 region from clade C human immunodeficiency virus-1 envelope

Vaccine Research Center, NIAID, National Institutes of Health, Room 4502, Bldg. 40, MSC-3005, 40 Convent Drive, Bethesda, MD 20892-3005, USA.
Vaccine (Impact Factor: 3.62). 07/2006; 24(23):4995-5002. DOI: 10.1016/j.vaccine.2006.03.083
Source: PubMed


To understand the cross-reactivity of antibodies directed against variable regions of human immunodeficiency virus-1 (HIV-1) envelope (Env), chimeric immunogens were prepared from different clades with modifications in variable regions, and the resulting neutralizing antibody response was evaluated. The V3-specific neutralization activity induced by a clade B immunogen was limited to clade B viruses and was blocked by a clade B V3 peptide, but not by analogous clade A or C V3 peptides. In contrast, the V3 response elicited by a clade C immunogen cross-reacted with sensitive clade B viruses. The V3 region from a clade C virus, when introduced into a clade B sequence, elicited cross-clade activity, which could be reversed by V3 peptides derived from clades A and C. Thus, the anti-V3 antibody response elicited by a clade C immunogen could cross-react with heterologous clade viruses. Additionally, we describe a V1-specific immune response that mediated neutralization limited to the homologous HIV IIIB isolate and may be partially responsible for the commonly observed strain-specific neutralization responses elicited by vaccine immunogens.

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    • "This observation that the elicitation of anti-V3 antibodies was not enhanced by both gp140-miniCD4 complex immunogens was also supported by HxB2-neutralization results. Sera from both the gp140-miniCD4, cross-linked or mixed, complex immunized groups neutralized HxB2, a virus that is not sensitive to anti-V3 antibodies [49], more potently (although without statistical significance) than sera from the group that was immunized by gp140 alone (Fig. 4). These data suggested that the structural alterations upon Env-CD4 protein binding and alterations upon gp140-miniCD4 interaction may differ concerning V3 loop exposure and subsequent V3-specific antibody elicitation. "
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    PLoS ONE 01/2012; 7(1):e30233. DOI:10.1371/journal.pone.0030233 · 3.23 Impact Factor
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    • "The V3 region of gp120, while variable in sequence, possesses conserved structural and immunologic features that induce neutralizing Abs (Gorny et al. 1993, Gorny et al. 2002, Stanfield et al. 2006, Bell et al. 2008, Wu et al. 2006). Numerous human anti-V3 mAbs have been produced and characterized, and while many of these mAbs are narrow in their focus, several have broad cross-clade neutralizing activity (Gorny et al. 2004, Gorny et al. 2006, Gorny et al. 2002, Binley et al. 2004, Bell et al. 2008, Pantophlet et al. 2008, Zolla-Pazner et al. 2008, Zolla-Pazner et al. 2004). "
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    • "Therefore, it is necessary to reduce the dose of each individual peptide [1] [2] [3] [4]. The V3 loop is the primary target for many neutralizing antibodies [5] [6] [7] and is involved in other aspects of infectivity. Thus, sequence changes in V3 affect chemokine receptor usage and therefore modulate the cell types that are infected [8] [9] [10]. "
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