Antibody recognition of the Pneumovirus fusion protein trimer interface

• DOI: 10.1371/journal.ppat.1008942
• Publication Date: 2020-10-09T17:35:04Z
• Authors: Jiachen Huang; Darren Diaz; Jarrod J. Mousa
• Keywords: Epitope mapping

Human metapneumovirus (hMPV) is a leading cause of viral respiratory infection in children, and can severe lower tract infants, the elderly, immunocompromised patients. However, there remain no licensed vaccines or specific treatments for hMPV infection. Although fusion (F) protein sole target neutralizing antibodies, immunological properties F poorly understood. To further define humoral immune response to protein, we isolated two new human monoclonal antibodies (mAbs), MPV458 MPV465. Both mAbs are vitro were determined unique antigenic site using competitive biolayer interferometry. We both MPV465 have higher affinity monomeric than trimeric F. was co-crystallized with F, mAb primarily interacts an alpha helix on F2 region protein. Surprisingly, major epitope lies within interface suggesting significant breathing must occur host recognition novel epitope. In addition, glycan interactions observed somatically mutated light chain framework residue. The data presented identifies epitope-based vaccine design, illustrates mechanism antibody neutralization glycoproteins.