title: Factors associated with the development of cross-reactive neutralizing antibodies during human immunodeficiency virus type 1 infection.
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.affiliation: Seattle Biomedical Research Institute, Seattle, Washington 98109, USA.
authors.forename: D Noah
authors.initials: DN
authors.lastname: Sather
authors.forename: Jakob
authors.initials: J
authors.lastname: Armann
authors.forename: Lance K
authors.initials: LK
authors.lastname: Ching
authors.forename: Angeliki
authors.initials: A
authors.lastname: Mavrantoni
authors.forename: George
authors.initials: G
authors.lastname: Sellhorn
authors.forename: Zachary
authors.initials: Z
authors.lastname: Caldwell
authors.forename: Xuesong
authors.initials: X
authors.lastname: Yu
authors.forename: Blake
authors.initials: B
authors.lastname: Wood
authors.forename: Steve
authors.initials: S
authors.lastname: Self
authors.forename: Spyros
authors.initials: S
authors.lastname: Kalams
authors.forename: Leonidas
authors.initials: L
authors.lastname: Stamatatos
mesh_terms: D003429:Cross Reactions; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology; D005260:Female; D015483:HIV Antibodies / Q000097:blood*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D009500:Neutralization Tests; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D000939:Epitopes; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus