Skip to main content
eScholarship
Open Access Publications from the University of California

Broad and Potent Neutralizing Antibodies Recognize the Silent Face of the HIV Envelope.

  • Author(s): 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
  • et al.
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.

Main Content
Current View