Antigenic conservation and immunogenicity of the HIV coreceptor binding site

Julie M. Decker, Frederic Bibollet-Ruche, Xiping Wei, Shuyi Wang, David Levy, Wenquan Wang, Eric Delaporte, Martine Peeters, Cynthia A. Derdeyn, Susan Allen, Eric Hunter, Michael S. Saag, James A. Hoxie, Beatrice H. Hahn, Peter D. Kwong, James E. Robinson, George M. Shaw

Research output: Contribution to journalArticle

Abstract

Immunogenic, broadly reactive epitopes of the HIV-1 envelope glycoprotein could serve as important targets of the adaptive humoral immune response in natural infection and, potentially, as components of an acquired immune deficiency syndrome vaccine. However, variability in exposed epitopes and a combination of highly effective envelope-cloaking strategies have made the identification of such epitopes problematic. Here, we show that the chemokine coreceptor binding site of HIV-1 from clade A, B, C, D, F, G, and H and circulating recombinant form (CRF)01, CRF02, and CRF11, elicits high titers of CD4-induced (CD4i) antibody during natural human infection and that these antibodies bind and neutralize viruses as divergent as HIV-2 in the presence of soluble CD4 (sCD4). 178 out of 189 (94%) HIV-1-infected patients had CD4i antibodies that neutralized sCD4-pretreated HIV-2 in titers (50% inhibitory concentration) as high as 1:143,000. CD4i monoclonal antibodies elicited by HIV-1 infection also neutralized HIV-2 pretreated with sCD4, and polyclonal antibodies from HIV-1-infected humans competed specifically with such monoclonal antibodies for binding. In vivo, variants of HIV-1 with spontaneously exposed coreceptor binding surfaces were detected in human plasma; these viruses were neutralized directly by CD4i antibodies. Despite remarkable evolutionary diversity among primate lentiviruses, functional constraints on receptor binding create opportunities for broad humoral immune recognition, which in turn serves to constrain the viral quasispecies.

Original languageEnglish (US)
Pages (from-to)1407-1419
Number of pages13
JournalJournal of Experimental Medicine
Volume201
Issue number9
DOIs
StatePublished - May 2 2005

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HIV-1
Binding Sites
HIV
HIV-2
Antibodies
Epitopes
Primate Lentiviruses
Monoclonal Antibodies
Viruses
Adaptive Immunity
Humoral Immunity
Infection
Chemokines
Inhibitory Concentration 50
HIV Infections
Glycoproteins
Acquired Immunodeficiency Syndrome
Vaccines
recombinant soluble CD4

ASJC Scopus subject areas

  • Immunology

Cite this

Decker, J. M., Bibollet-Ruche, F., Wei, X., Wang, S., Levy, D., Wang, W., ... Shaw, G. M. (2005). Antigenic conservation and immunogenicity of the HIV coreceptor binding site. Journal of Experimental Medicine, 201(9), 1407-1419. https://doi.org/10.1084/jem.20042510

Antigenic conservation and immunogenicity of the HIV coreceptor binding site. / Decker, Julie M.; Bibollet-Ruche, Frederic; Wei, Xiping; Wang, Shuyi; Levy, David; Wang, Wenquan; Delaporte, Eric; Peeters, Martine; Derdeyn, Cynthia A.; Allen, Susan; Hunter, Eric; Saag, Michael S.; Hoxie, James A.; Hahn, Beatrice H.; Kwong, Peter D.; Robinson, James E.; Shaw, George M.

In: Journal of Experimental Medicine, Vol. 201, No. 9, 02.05.2005, p. 1407-1419.

Research output: Contribution to journalArticle

Decker, JM, Bibollet-Ruche, F, Wei, X, Wang, S, Levy, D, Wang, W, Delaporte, E, Peeters, M, Derdeyn, CA, Allen, S, Hunter, E, Saag, MS, Hoxie, JA, Hahn, BH, Kwong, PD, Robinson, JE & Shaw, GM 2005, 'Antigenic conservation and immunogenicity of the HIV coreceptor binding site', Journal of Experimental Medicine, vol. 201, no. 9, pp. 1407-1419. https://doi.org/10.1084/jem.20042510
Decker, Julie M. ; Bibollet-Ruche, Frederic ; Wei, Xiping ; Wang, Shuyi ; Levy, David ; Wang, Wenquan ; Delaporte, Eric ; Peeters, Martine ; Derdeyn, Cynthia A. ; Allen, Susan ; Hunter, Eric ; Saag, Michael S. ; Hoxie, James A. ; Hahn, Beatrice H. ; Kwong, Peter D. ; Robinson, James E. ; Shaw, George M. / Antigenic conservation and immunogenicity of the HIV coreceptor binding site. In: Journal of Experimental Medicine. 2005 ; Vol. 201, No. 9. pp. 1407-1419.
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