title: Antibody specificities associated with neutralization breadth in plasma from human immunodeficiency virus type 1 subtype C-infected blood donors.
abstract: Defining the specificities of the anti-human immunodeficiency virus type 1 (HIV-1) envelope antibodies able to mediate broad heterologous neutralization will assist in identifying targets for an HIV-1 vaccine. We screened 70 plasmas from chronically HIV-1-infected individuals for neutralization breadth. Of these, 16 (23%) were found to neutralize 80% or more of the viruses tested. Anti-CD4 binding site (CD4bs) antibodies were found in almost all plasmas independent of their neutralization breadth, but they mainly mediated neutralization of the laboratory strain HxB2 with little effect on the primary virus, Du151. Adsorption with Du151 monomeric gp120 reduced neutralizing activity to some extent in most plasma samples when tested against the matched virus, although these antibodies did not always confer cross-neutralization. For one plasma, this activity was mapped to a site overlapping the CD4-induced (CD4i) epitope and CD4bs. Anti-membrane-proximal external region (MPER) (r = 0.69; P < 0.001) and anti-CD4i (r = 0.49; P < 0.001) antibody titers were found to be correlated with the neutralization breadth. These anti-MPER antibodies were not 4E10- or 2F5-like but spanned the 4E10 epitope. Furthermore, we found that anti-cardiolipin antibodies were correlated with the neutralization breadth (r = 0.67; P < 0.001) and anti-MPER antibodies (r = 0.6; P < 0.001). Our study suggests that more than one epitope on the envelope glycoprotein is involved in the cross-reactive neutralization elicited during natural HIV-1 infection, many of which are yet to be determined, and that polyreactive antibodies are possibly involved in this phenomenon.
authors: AIDS Virus Research Unit, National Institute for Communicable Diseases, Johannesburg, Private Bag X4, Sandringham 2131, Johannesburg, South Africa.
authors: Elin S
authors: ES
authors: Gray
authors: Natasha
authors: N
authors: Taylor
authors: Diane
authors: D
authors: Wycuff
authors: Penny L
authors: PL
authors: Moore
authors: Georgia D
authors: GD
authors: Tomaras
authors: Constantinos Kurt
authors: CK
authors: Wibmer
authors: Adrian
authors: A
authors: Puren
authors: Allan
authors: A
authors: DeCamp
authors: Peter B
authors: PB
authors: Gilbert
authors: Blake
authors: B
authors: Wood
authors: David C
authors: DC
authors: Montefiori
authors: James M
authors: JM
authors: Binley
authors: George M
authors: GM
authors: Shaw
authors: Barton F
authors: BF
authors: Haynes
authors: John R
authors: JR
authors: Mascola
authors: Lynn
authors: L
authors: Morris
mesh_terms: D017153:Antibodies, Anticardiolipin / Q000097:blood; D000918:Antibody Specificity; D001782:Blood Donors; D003429:Cross Reactions; D018604:Epitope Mapping; D015483:HIV Antibodies / Q000097:blood*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D009500:Neutralization Tests
chemical_list: D017153:Antibodies, Anticardiolipin; D015483:HIV Antibodies