Early Antibody Lineage Diversification and Independent Limb Maturation Lead to Broad HIV-1 Neutralization Targeting the Env High-Mannose Patch.

Autor:	MacLeod DT; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, New York, NY 10038, USA., Choi NM; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, New York, NY 10038, USA., Briney B; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA., Garces F; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA., Ver LS; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, New York, NY 10038, USA., Landais E; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, New York, NY 10038, USA., Murrell B; Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA., Wrin T; Monogram Biosciences Inc., San Francisco, CA, 94080, USA., Kilembe W; Zambia-Emory HIV Research Project, Lusaka, Zambia., Liang CH; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA., Ramos A; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, New York, NY 10038, USA., Bian CB; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, New York, NY 10038, USA., Wickramasinghe L; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, New York, NY 10038, USA., Kong L; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA., Eren K; Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA., Wu CY; Genomics Research Center, Academia Sinica, Taipei 115, Taiwan., Wong CH; Genomics Research Center, Academia Sinica, Taipei 115, Taiwan., Kosakovsky Pond SL; Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA., Wilson IA; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA., Burton DR; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA., Poignard P; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, New York, NY 10038, USA; Institut de Biologie Structurale, Université Grenoble Alpes, CEA, CNRS, 38044 Grenoble, France. Electronic address: poignard@scripps.edu.
Jazyk:	angličtina
Zdroj:	Immunity [Immunity] 2016 May 17; Vol. 44 (5), pp. 1215-26.
DOI:	10.1016/j.immuni.2016.04.016
Abstrakt:	The high-mannose patch on HIV Env is a preferred target for broadly neutralizing antibodies (bnAbs), but to date, no vaccination regimen has elicited bnAbs against this region. Here, we present the development of a bnAb lineage targeting the high-mannose patch in an HIV-1 subtype-C-infected donor from sub-Saharan Africa. The Abs first acquired autologous neutralization, then gradually matured to achieve breadth. One Ab neutralized >47% of HIV-1 strains with only ∼11% somatic hypermutation and no insertions or deletions. By sequencing autologous env, we determined key residues that triggered the lineage and participated in Ab-Env coevolution. Next-generation sequencing of the Ab repertoire showed an early expansive diversification of the lineage followed by independent maturation of individual limbs, several of them developing notable breadth and potency. Overall, the findings are encouraging from a vaccine standpoint and suggest immunization strategies mimicking the evolution of the entire high-mannose patch and promoting maturation of multiple diverse Ab pathways. (Copyright © 2016 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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