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J Virol. 2009 Jan;83(2):757-69. doi: 10.1128/JVI.02036-08. Epub 2008 Nov 5.

Factors associated with the development of cross-reactive neutralizing antibodies during human immunodeficiency virus type 1 infection.

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1
Seattle Biomedical Research Institute, Seattle, Washington 98109, USA.

Erratum in

  • J Virol. 2009 May;83(9):4713-5.

Abstract

The characterization of the cross-reactive, or heterologous, neutralizing antibody responses developed during human immunodeficiency virus type 1 (HIV-1) infection and the identification of factors associated with their generation are relevant to the development of an HIV vaccine. We report that in healthy HIV-positive, antiretroviral-naïve subjects, the breadth of plasma heterologous neutralizing antibody responses correlates with the time since infection, plasma viremia levels, and the binding avidity of anti-Env antibodies. Anti-CD4-binding site antibodies are responsible for the exceptionally broad cross-neutralizing antibody responses recorded only in rare plasma samples. However, in most cases examined, antibodies to the variable regions and to the CD4-binding site of Env modestly contributed in defining the overall breadth of these responses. Plasmas with broad cross-neutralizing antibody responses were identified that targeted the gp120 subunit, but their precise epitopes mapped outside the variable regions and the CD4-binding site. Finally, although several plasmas were identified with cross-neutralizing antibody responses that were not directed against gp120, only one plasma with a moderate breadth of heterologous neutralizing antibody responses contained cross-reactive neutralizing antibodies against the 4E10 epitope, which is within the gp41 transmembrane subunit. Overall, our study indicates that more than one pathway leads to the development of broad cross-reactive neutralizing antibodies during HIV infection and that the virus continuously escapes their action.

PMID:
18987148
PMCID:
PMC2612355
DOI:
10.1128/JVI.02036-08
[Indexed for MEDLINE]
Free PMC Article
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