학술논문
Broad and Potent Neutralizing Antibodies Recognize the Silent Face of the HIV Envelope
Document Type
article
Author
Schoofs, Till; Barnes, Christopher O; Suh-Toma, Nina; Golijanin, Jovana; Schommers, Philipp; Gruell, Henning; West, Anthony P; Bach, Franziska; Lee, Yu Erica; Nogueira, Lilian; Georgiev, Ivelin S; Bailer, Robert T; Czartoski, Julie; Mascola, John R; Seaman, Michael S; McElrath, M Juliana; Doria-Rose, Nicole A; Klein, Florian; Nussenzweig, Michel C; Bjorkman, Pamela J
Source
Immunity. 50(6)
Subject
Language
Abstract
Broadly neutralizing antibodies (bNAbs) against HIV-1 envelope (Env) inform vaccine design and are potential therapeutic agents. We identified SF12 and related bNAbs with up to 62% neutralization breadth from an HIV-infected donor. SF12 recognized a glycan-dominated epitope on Env's silent face and was potent against clade AE viruses, which are poorly covered by V3-glycan bNAbs. A 3.3Å cryo-EM structure of a SF12-Env trimer complex showed additional contacts to Env protein residues by SF12 compared with VRC-PG05, the only other known donor-derived silentface antibody, explaining SF12's increased neutralization breadth, potency, and resistance to Env mutation routes. Asymmetric binding of SF12 was associated with distinct N-glycan conformations across Env protomers, demonstrating intra-Env glycan heterogeneity. Administrating SF12 to HIV-1-infected humanized mice suppressed viremia and selected for viruses lacking the N448gp120 glycan. Effective bNAbs can therefore be raised against HIV-1 Env's silent face, suggesting their potential for HIV-1 prevention, therapy, and vaccine development.