|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|
|Date Published||2017 Jan 27|
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.
|Alternate Journal||Sci Immunol|