Novel advances in parainfluenza virus 3 neutralization through antibodies targeting hemagglutinin-neuraminidase.

Abstract Parainfluenza virus 3 (PIV3) remains to be a global burden to infants, the elderly, and immunocompromised individuals. With no approved therapeutics or vaccines, PIV3 continues to cause a large portion of the lower respiratory illness hospitalizations in young children. Similar to other paramyxoviruses, PIV3 utilizes two structural proteins, the fusion (F) protein and the hemagglutinin-neuraminidase (HN) protein, for viral fusion and entry. Here, we characterize newly identified human monoclonal antibodies (mAbs) targeting HN on the PIV3 virion, with EC 50values ranging from 9ng/mL to 21ng/mL. The mAbs were tested for neutralization of PIV3 and all were determined to have an IC 50values ranging from 11ng/mL to 450ng/mL. Utilizing biolayer interferometry, we conducted a competitive epitope mapping study and found the mAbs targeted three major epitopes on the HN protein with some competitive binding between multiple sites, suggesting these epitopes are within close proximity of each other. mAbs binding to one particular site had significantly low IC 50values ranging from 11ng/mL to 120ng/mL. We have established a PIV3 infection model in Golden Syrian hamsters and are currently testing mAbs from each epitope for prevention of viral replication in the lungs and airways. Due to the similarities between the HN protein amongst different parainfluenza virus subtypes, we plan to study the potential cross-neutralizing capabilities of these mAbs against other parainfluenza virus subtypes. Supported by grants from NIH (R01 AI143865)