The structural basis of protective and nonprotective human monoclonal antibodies targeting the parainfluenza virus type 3 hemagglutinin-neuraminidase.

Parainfluenza virus 3 (PIV3) infection poses a substantial risk to vulnerable groups including infants, the elderly, and immunocompromised individuals, and lacks effective treatments or vaccines. This study focuses on targeting the hemagglutinin-neuraminidase (HN) protein, a structural glycoprotein of PIV3 critical for viral infection and egress. With the objective of targeting these activities of HN, we identified eight neutralizing human monoclonal antibodies (mAbs) with potent effects on viral neutralization, cell-cell fusion inhibition, and complement deposition.

Broadly Protective Neuraminidase-Based Influenza Vaccines and Monoclonal Antibodies: Target Epitopes and Mechanisms of Action.

Neuraminidase (NA) is an important surface protein on influenza virions, playing an essential role in the viral life cycle and being a key target of the immune system. Despite the importance of NA-based immunity, current vaccines are focused on the hemagglutinin (HA) protein as the target for protective antibodies, and the amount of NA is not standardized in virion-based vaccines. Antibodies targeting NA are predominantly protective, reducing infection severity and viral shedding.

Differential Recognition of Computationally Optimized H3 Hemagglutinin Influenza Vaccine Candidates by Human Antibodies.

Among circulating influenza viruses in humans, H3N2 viruses typically evolve faster than other subtypes and have caused disease in millions of people since emerging in 1968. Computationally optimized broadly reactive antigen (COBRA) technology is one strategy to broaden vaccine-elicited antibody responses among influenza subtypes. In this study, we determined the structural integrity of an H3N2 COBRA hemagglutinin (HA), TJ5, and we probed the antigenic profile of several H3N2 COBRA HAs by assessing recognition of these immunogens by human B cells from seasonally vaccinated human subjects.

The Pre-Existing Human Antibody Repertoire to Computationally Optimized Influenza H1 Hemagglutinin Vaccines.

Computationally optimized broadly reactive Ag (COBRA) hemagglutinin (HA) immunogens have previously been generated for several influenza subtypes to improve vaccine-elicited Ab breadth. As nearly all individuals have pre-existing immunity to influenza viruses, influenza-specific memory B cells will likely be recalled upon COBRA HA vaccination. We determined the epitope specificity and repertoire characteristics of pre-existing human B cells to H1 COBRA HA Ags.