Human immunodeficiency virus type 1 gp41 antibodies that mask membrane proximal region epitopes: antibody binding kinetics, induction, and potential for regulation in acute infection.
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.
Alam
S Munir
SM
Human Vaccine Institute, Box 3258, Duke University Medical Center, MSRBII Bldg., Room 4042, Durham, NC 27710, USA. alam0004@mc.duke.edu
Scearce
Richard M
RM
Parks
Robert J
RJ
Plonk
Kelly
K
Plonk
Steven G
SG
Sutherland
Laura L
LL
Gorny
Miroslaw K
MK
Zolla-Pazner
Susan
S
Vanleeuwen
Stacie
S
Moody
M Anthony
MA
Xia
Shi-Mao
SM
Montefiori
David C
DC
Tomaras
Georgia D
GD
Weinhold
Kent J
KJ
Karim
Salim Abdool
SA
Hicks
Charles B
CB
Liao
Hua-Xin
HX
Robinson
James
J
Shaw
George M
GM
Haynes
Barton F
BF
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
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D008055:Lipids; C514787:gp41 protein, Human immunodeficiency virus 1