Human antibody recognition of antigenic site IV on Pneumovirus fusion proteins

• DOI: 10.1371/journal.ppat.1006837
• Publication Date: 2018-02-22T19:12:38Z
• Authors: Jarrod J. Mousa; Elad Binshtein; Stacey Human; Rachel H. Fong; Gabriela Alvarado; Benjamin J. Doranz; Martin L. Moore; Melanie D. Ohi; James E. Crowe
• Keywords: Epitope mapping

Respiratory syncytial virus (RSV) is a major human pathogen that infects the majority of children by two years age. The RSV fusion (F) protein primary target antibodies, and it has several antigenic regions capable inducing neutralizing antibodies. Antigenic site IV preserved in both pre-fusion post-fusion conformations F. Antibodies to have been described bind neutralize metapneumovirus (hMPV). To explore diversity binding modes at IV, we generated panel four new monoclonal antibodies (mAbs) competition-binding suggested mAbs IV. Mutagenesis experiments revealed neutralization (3M3 6F18) depended on arginine (R) residue R429. We discovered R429-independent (17E10 2N6) this neutralized an R429A mutant strain, one these (17E10) hMPV. determine mechanism cross-reactivity, performed competition-binding, recombinant mutagenesis, peptide binding, electron microscopy experiments. It was determined cross-reactive mAb 17E10 binds F with pose similar 101F, which may be indicative cross-reactivity hMPV data presented provide concepts immune recognition vaccine design, as describe novel idea influence between Characterization epitope bound inform design pan-Pneumovirus vaccine.