Potent and broad HIV-neutralizing antibodies in memory B cells and plasma.

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TitlePotent and broad HIV-neutralizing antibodies in memory B cells and plasma.
Publication TypeJournal Article
Year of Publication2017
AuthorsWilliams, LTD, Ofek, GA, Schätzle, S, McDaniel, JR, Lu, X, Nicely, NI, Wu, L, Lougheed, CS, Bradley, T, Louder, MK, McKee, K, Bailer, RT, O'Dell, S, Georgiev, IS, Seaman, MS, Parks, RJ, Marshall, DJ, Anasti, K, Yang, G, Nie, X, Tumba, NL, Wiehe, K, Wagh, K, Korber, B, Kepler, TB, S Alam, M, Morris, L, Kamanga, G, Cohen, MS, Bonsignori, M, Xia, S-M, Montefiori, DC, Kelsoe, G, Gao, F, Mascola, JR, M Moody, A, Saunders, KO, Liao, H-X, Tomaras, GD, Georgiou, G, Haynes, BF
JournalSci Immunol
Volume2
Issue7
Date Published2017 Jan 27
ISSN2470-9468
Abstract

Induction of broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development. Antibody 10E8, reactive with the distal portion of the membrane-proximal external region (MPER) of HIV-1 gp41, is broadly neutralizing. However, the ontogeny of distal MPER antibodies and the relationship of memory B cell to plasma bnAbs are poorly understood. HIV-1-specific memory B cell flow sorting and proteomic identification of anti-MPER plasma antibodies from an HIV-1-infected individual were used to isolate broadly neutralizing distal MPER bnAbs of the same B cell clonal lineage. Structural analysis demonstrated that antibodies from memory B cells and plasma recognized the envelope gp41 bnAb epitope in a distinct orientation compared with other distal MPER bnAbs. The unmutated common ancestor of this distal MPER bnAb was autoreactive, suggesting lineage immune tolerance control. Construction of chimeric antibodies of memory B cell and plasma antibodies yielded a bnAb that potently neutralized most HIV-1 strains.

DOI10.1126/sciimmunol.aal2200
Alternate JournalSci Immunol
PubMed ID28783671