Potent Cross-neutralizing Antibodies Reveal Vulnerabilities of Henipavirus Fusion Glycoprotein.

ABSTRACT: Hendra and Nipah viruses (HNVs), zoonotic paramyxoviruses with >50% case fatality rates, cause fatal encephalitis and respiratory disease, yet lack approved therapies. Here, nine rhesus-derived monoclonal antibodies (mAbs) targeting the fusion glycoprotein (F) prefusion conformation are developed. Four mAbs exhibit first-rate cross-neutralization against HNVs, with two showing synergistic potency when combined with attachment glycoprotein (G)-specific mAbs. Single-dose administration of mAbs confers robust protection against lethal Nipah virus challenge in hamsters. Structural insights reveal that 8 of the 9 potent mAbs adopt a human IGHV4-59-like framework with protruding CDRH3 loops, forming pushpin-shaped paratopes that stabilize the prefusion F-trimer by occupying vulnerable interproto

SUBMITTER: Ren Y 

PROVIDER: S-EPMC12279222 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature