

Title | Potent and broad HIV-neutralizing antibodies in memory B cells and plasma. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Williams, 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 |
Journal | Sci Immunol |
Volume | 2 |
Issue | 7 |
Date Published | 2017 Jan 27 |
ISSN | 2470-9468 |
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. |
DOI | 10.1126/sciimmunol.aal2200 |
Alternate Journal | Sci Immunol |
PubMed ID | 28783671 |