A potently neutralizing site III-specific human antibody prevents human metapneumovirus replication in vivo

Abstract

Abstract Human metapneumovirus (hMPV) is a leading cause of lower respiratory tract infection in infants and children, yet there is currently no vaccine available for prevention of hMPV disease. hMPV has three surface proteins: the small hydrophobic, the attachment, and the fusion (F) protein. The hMPV F protein is the sole target of neutralizing antibodies. To develop new therapeutics for disease intervention and to inform the development of an effective vaccine, we isolated several new human monoclonal antibodies (mAbs) to the hMPV F protein. A subset of these mAbs were determined to be neutralizing by a plaque reduction assay. The neutralizing mAbs bind to all four subgroups of the hMPV F protein, and neutralize viruses from both the A and B genotypes. We conducted epitope binning assays on the OctetRED384 system to determine the antigenic targets of each mAb. Three of the four mAbs (196, 314, 201) bind near the previously discovered mAb DS7. One mAb, MPV364, competes with the site III mAbs MPE8 and 25P13, yet unlike these mAbs, MPV364 does not cross-react with the respiratory syncytial virus F protein. MPV364 exhibits potent and broadly neutralizing activity below 20 ng/mL. We examined the therapeutic efficacy of MPV364 to prevent replication of hMPV in vivo and found a reduction in lung viral titers. These data suggest antigenic site III on the hMPV F protein elicits potently neutralizing mAbs, and should be incorporated into future vaccine candidates. Furthermore, MPV364 should be further examined for protection from hMPV disease in additional animal models of infection.