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Broad HIV-1 neutralization mediated by CD4-binding site antibodies

Abstract

We have identified several patient sera showing potent and broad HIV-1 neutralization. Using antibody adsorption and elution from selected gp120 variants, the neutralizing specificities of the two most broadly reactive sera were mapped to the primary receptor CD4–binding region of HIV-1 gp120. Novel antibodies to the CD4-binding site are elicited in some HIV-1–infected individuals, and new approaches to present this conserved region of gp120 to the immune system may result in improved vaccine immunogens.

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Figure 1: Adsorption of sera with gp120WT and CD4-binding site mutant proteins.
Figure 2: Analysis of antibodies eluted from Env protein beads and after additional adsorption to enrich for CD4-binding site antibodies.

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Acknowledgements

This research was supported in part by the Intramural Research Program of the Vaccine Research Center and Division of Intramural Research, National Institute of Allergy and Infectious Diseases, US National Institutes of Health. G.M.S. and R.T.W. were supported in part by a grant from the Bill & Melinda Gates Foundation Grand Challenges initiative. R.T.W. also receives funding from the International AIDS Vaccine Initiative. We thank P. Kwong and G. Nabel for helpful suggestions; L. Kong for the core molecular surface figure; L. Chen (Vaccine Research Center) for providing the Fab fragment of F105, which was obtained from the laboratory of M. Posner (Dana Farber Cancer Institute); D. Burton (Scripps Research Institute) for mAb IgG1b12; H. Katinger (Polymun Scientific Inc.) for mAb 2G12; S. Zolla-Pazner (New York University School of Medicine) for mAb 447-52D; J. Sodroski and D. Gabuzda (Dana Farber Cancer Institute), J. Overbaugh (Fred Hutchinson Cancer Research Center), L. Morris (National Institute of Communicable Diseases), D. Montefiori (Duke University), J. Binley (Torrey Pines Institute for Molecular Sciences), L. Stamatatos (Seattle Biomedical Research Institute) and V. Polonis and F. McCutchan (U.S. Military Research Program) for providing virus isolates or functional Env plasmids; other members of the Wyatt laboratory who contributed ideas or reagents to the study; and B. Hartman and M. Cichanowski for help in preparation of the figures.

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Correspondence to Richard T Wyatt.

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Supplementary Figs. 1 & 2, Supplementary Tables 1 & 2, Supplementary Methods (PDF 1114 kb)

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Li, Y., Migueles, S., Welcher, B. et al. Broad HIV-1 neutralization mediated by CD4-binding site antibodies. Nat Med 13, 1032–1034 (2007). https://doi.org/10.1038/nm1624

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