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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Williams, LD; Ofek, G; 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; Munir Alam, S; Morris, L; Kamanga, G; Cohen, MS; Bonsignori, M; Xia, S-M; Montefiori, DC; Kelsoe, G; Gao, F; Mascola, JR; Moody, MA; Saunders, KO; Liao, H-X; Tomaras, GD; Georgiou, G; Haynes, BF

Published Date

  • January 2017

Published In

Volume / Issue

  • 2 / 7

PubMed ID

  • 28783671

Pubmed Central ID

  • 28783671

Electronic International Standard Serial Number (EISSN)

  • 2470-9468

International Standard Serial Number (ISSN)

  • 2470-9468

Digital Object Identifier (DOI)

  • 10.1126/sciimmunol.aal2200

Language

  • eng