title: Human immunodeficiency virus type 1 gp41 antibodies that mask membrane proximal region epitopes: antibody binding kinetics, induction, and potential for regulation in acute infection.
abstract: Two human monoclonal antibodies (MAbs) (2F5 and 4E10) against the human immunodeficiency virus type 1 (HIV-1) envelope g41 cluster II membrane proximal external region (MPER) broadly neutralize HIV-1 primary isolates. However, these antibody specificities are rare, are not induced by Env immunization or HIV-1 infection, and are polyspecific and also react with lipids such as cardiolipin or phosphatidylserine. To probe MPER anti-gp41 antibodies that are produced in HIV-1 infection, we have made two novel murine MAbs, 5A9 and 13H11, against HIV-1 gp41 envelope that partially cross-blocked 2F5 MAb binding to Env but did not neutralize HIV-1 primary isolates or bind host lipids. Competitive inhibition assays using labeled 13H11 MAb and HIV-1-positive patient plasma samples demonstrated that cluster II 13H11-blocking plasma antibodies were made in 83% of chronically HIV-1 infected patients and were acquired between 5 to 10 weeks after acute HIV-1 infection. Both the mouse 13H11 MAb and the three prototypic cluster II human MAbs (98-6, 126-6, and 167-D) blocked 2F5 binding to gp41 epitopes to variable degrees; the combination of 98-6 and 13H11 completely blocked 2F5 binding. These data provide support for the hypothesis that in some patients, B cells make nonneutralizing cluster II antibodies that may mask or otherwise down-modulate B-cell responses to immunogenic regions of gp41 that could be recognized by B cells capable of producing antibodies like 2F5.
authors.affiliation: Human Vaccine Institute, Box 3258, Duke University Medical Center, MSRBII Bldg., Room 4042, Durham, NC 27710, USA. alam0004@mc.duke.edu
authors.forename: S Munir
authors.initials: SM
authors.lastname: Alam
authors.forename: Richard M
authors.initials: RM
authors.lastname: Scearce
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Parks
authors.forename: Kelly
authors.initials: K
authors.lastname: Plonk
authors.forename: Steven G
authors.initials: SG
authors.lastname: Plonk
authors.forename: Laura L
authors.initials: LL
authors.lastname: Sutherland
authors.forename: Miroslaw K
authors.initials: MK
authors.lastname: Gorny
authors.forename: Susan
authors.initials: S
authors.lastname: Zolla-Pazner
authors.forename: Stacie
authors.initials: S
authors.lastname: Vanleeuwen
authors.forename: M Anthony
authors.initials: MA
authors.lastname: Moody
authors.forename: Shi-Mao
authors.initials: SM
authors.lastname: Xia
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.forename: Kent J
authors.initials: KJ
authors.lastname: Weinhold
authors.forename: Salim Abdool
authors.initials: SA
authors.lastname: Karim
authors.forename: Charles B
authors.initials: CB
authors.lastname: Hicks
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
authors.forename: James
authors.initials: J
authors.lastname: Robinson
authors.forename: George M
authors.initials: GM
authors.lastname: Shaw
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000302:isolation & purification; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D008055:Lipids / Q000276:immunology; D051379:Mice; D009500:Neutralization Tests; D011485:Protein Binding
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D008055:Lipids; C514787:gp41 protein, Human immunodeficiency virus 1