| 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. |
| Authors | D Noah Sather, Jakob Armann, Lance K Ching, Angeliki Mavrantoni, George Sellhorn, Zachary Caldwell, Xuesong Yu, Blake Wood, Steve Self, Spyros Kalams, Leonidas Stamatatos
(Affiliation: Seattle Biomedical Research Institute, Seattle, Washington 98109, USA.)
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| Journal | Journal of virology
(J Virol)
Vol. 83
Issue 2
Pg. 757-69
(Jan 2009)
ISSN: 1098-5514 United States |
| PMID | 18987148
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Epitopes
- HIV Antibodies
- env Gene Products, Human Immunodeficiency Virus
|
| Topics |
- Cross Reactions
- Epitope Mapping
- Epitopes
(immunology)
- Female
- HIV Antibodies
(blood)
- HIV Infections
(immunology)
- HIV-1
(immunology)
- Humans
- Male
- Neutralization Tests
- env Gene Products, Human Immunodeficiency Virus
(immunology)
|
