Fab-dimerized glycan-reactive antibodies neutralize HIV and are prevalent in humans and rhesus macaques [article]

Wilton B Williams, Ryan Meyerhoff, Robert J Edwards, Hui Li, Nathan Nicely, Rory Henderson, Ye Zhou, Katarzyna Janowska, Katayoun Mansouri, Kartik Manne, Victoria Stalls, Allen L Hsu (+31 others)
2020 bioRxiv   pre-print
The HIV-1 envelope (Env) is comprised by mass of over 50% glycans. A goal of HIV-1 vaccine development is the induction of Env glycan-reactive broadly neutralizing antibodies (bnAbs). The 2G12 bnAb recognizes an Env glycan cluster using a unique variable heavy (VH) domain-swapped conformation that results in fragment antigen-binding (Fab) dimerization. Here we describe Fab-dimerized glycan (FDG)-reactive antibodies without VH-swapped domains from simian-human immunodeficiency virus
more » ... virus (SHIV)-infected macaques that neutralized heterologous HIV-1 isolates. FDG precursors were boosted by vaccination in macaques, and were present in HIV-1-naïve humans with an average estimated frequency of one per 340,000 B cells. These data demonstrate frequent HIV-1 Env glycan-reactive bnAb B cell precursors in macaques and humans and reveal a novel strategy for their induction by vaccination.
doi:10.1101/2020.06.30.178921 fatcat:no33ns5r6vg7tfobbid6xavhea