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. 2010 May 26:28 Suppl 2:B8-12.
doi: 10.1016/j.vaccine.2009.07.085.

Epitope specificities of broadly neutralizing plasmas from HIV-1 infected subjects

D Noah Sather  1 , Leonidas Stamatatos
Affiliations

Epitope specificities of broadly neutralizing plasmas from HIV-1 infected subjects

D Noah Sather et al. Vaccine. .

Abstract

The characterization of the cross-reactive, or heterologous, neutralizing antibody (NAb) responses developed during HIV-1-infection is relevant to the development of an HIV vaccine. Here we summarize our recently published study where we characterized the cross-reactive NAb responses in two cohorts of anti-retroviral naïve, healthy, acute and chronically HIV-infected subjects (N=39) and present new information regarding epitope specificities. We determined that anti-CD4-binding site antibodies are responsible for the exceptionally broad cross-neutralizing antibody responses recorded only in rare plasma samples. Plasma from three subjects with moderate to high breadth of heterologous neutralizing antibody responses contained antibodies targeting the 4E10-epitope within the gp41 transmembrane subunit, and plasma from one these three subjects also contained antibodies against the 2F5 epitope. However, In most subjects with moderate to high breadth of cross-neutralization, the specificities of their NAb responses remain unknown. Overall, our study indicates that more than one pathway leads to the development of broad cross-reactive NAbs during HIV-infection.

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Figures

Figure 1
Figure 1
(a) Frequency of broadly cross-reactive NAb responses in two HIV+ cohorts. Percent breadth is calculated as the number of isolates out of the total isolates tested that each plasma neutralized. (b) Cross-clade neutralization of subject VC10042 against selected clade A, B, and C viruses. Red line indicates the 50% reduction in neutralization (IC50).
Figure 2
Figure 2
Characterization of MPER-directed antibodies in plasmas (a) VC10028, (b) CC1782, and (c) VC20013, as well as mAb 4E10 (d). Plasmas were tested in an ELISA format with 4E10 peptide variants as the antigen. The sequence of the 4E10 epitope is noted in panel (e), and arrows indicate amino acid positions that were individually changed to alanine for epitope analysis.
Figure 3
Figure 3
Schematic of the differential adsorption of HIV+ plasma with gp120wt or gp120bs - coupled beads.
See this image and copyright information in PMC

References

    1. Hu SL, Stamatatos L. Prospects of HIV Env modification as an approach to HIV vaccine design. Current HIV research. 2007 Nov;5(6):507–13. - PubMed
    1. Brown BK, Wieczorek L, Sanders-Buell E, Borges AR, Robb ML, Birx DL, et al. Cross-clade neutralization patterns among HIV-1 strains from the six major clades of the pandemic evaluated and compared in two different models. Virology. 2008 Jun 5;375(2):529–38. - PubMed
    1. Kostrikis LG, Cao Y, Ngai H, Moore JP, Ho DD. Quantitative analysis of serum neutralization of human immunodeficiency virus type 1 from subtypes A, B, C, D, E, F, and I: lack of direct correlation between neutralization serotypes and genetic subtypes and evidence for prevalent serum-dependent infectivity enhancement. J Virol. 1996 Jan;70(1):445–58. - PMC - PubMed
    1. Moore JP, Cao Y, Leu J, Qin L, Korber B, Ho DD. Inter- and intraclade neutralization of human immunodeficiency virus type 1: genetic clades do not correspond to neutralization serotypes but partially correspond to gp120 antigenic serotypes. J Virol. 1996 Jan;70(1):427–44. - PMC - PubMed
    1. Tomaras GD, Yates NL, Liu P, Qin L, Fouda GG, Chavez LL, et al. Initial B Cell Responses to Transmitted HIV-1: Virion-Binding IgM and IgG Antibodies Followed by Plasma Anti-gp41 Antibodies with Ineffective Control of Initial Viremia. J Virol. 2008 Oct 8; - PMC - PubMed

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