Abstract
ABSTRACTThe influenza virus neuraminidase (NA) is becoming a focus for novel vaccine designs. However, the epitopes of human anti-NA antibodies have been poorly defined. Using a panel of 10 anti-N2 monoclonal antibodies (MAbs) that bind the H3N2 virus A/Switzerland/9715293/2013, we generated five escape mutant viruses. These viruses contained mutations K199E/T, E258K, A272D, and S331N. We found that mutations at K199 and E258 had the largest impact on MAb binding, NA inhibition and neutralization activity. In addition, a natural isolate from the 2017-2018 season was found to contain the E258K mutation and was resistant to numerous antibodies tested. The mutation S331N, was identified in virus passaged in the presence of antibody; however, it had little impact on MAb activity and greatly decreased viral fitness. This information aids in identifying novel human MAb epitopes on the N2 and helps with the detection of antigenically drifted NAs.IMPORTANCE The influenza virus neuraminidase is an emerging target for universal influenza virus vaccines. However, in contrast to influenza virus hemagglutinin, we know little about antibody epitopes and antigenic sites on the neuraminidase. Characterizing and defining these sites is aiding vaccine development and helping to understand antigenic drift of NA.
Highlights
The influenza virus neuraminidase (NA) is becoming a focus for novel vaccine designs
To accurately designate monoclonal antibodies (MAbs) epitopes on the N2, we began by determining whether the mutations found using our panel of antibodies overlapped with those previously identified
The S331N escape mutant viruses (EMVs) did not become resistant to any MAbs in the panel
Summary
The influenza virus neuraminidase (NA) is becoming a focus for novel vaccine designs. Using a panel of 10 anti-N2 monoclonal antibodies (MAbs) that bind the H3N2 virus A/Switzerland/9715293/2013, we generated five escape mutant viruses. These viruses contained mutations K199E/T, E258K, A272D, and S331N. The mutation S331N, was identified in virus passaged in the presence of antibody; it had little impact on MAb activity and greatly decreased viral fitness This information aids in identifying novel human MAb epitopes on the N2 and helps with the detection of antigenically drifted NAs. IMPORTANCE The influenza virus neuraminidase is an emerging target for universal influenza virus vaccines. In contrast to influenza virus hemagglutinin, we know little about antibody epitopes and antigenic sites on the neuraminidase Characterizing and defining these sites is aiding vaccine development and helping to understand antigenic drift of NA. An understanding of the anti-N2 antibody response can provide insights for rational vaccine design, which may be critical for future NA containing vaccines
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