Selection and analysis of antigenic variants of the neuraminidase of N2 influenza viruses with monoclonal antibodies

Abstract

Antigenic variants of the neuraminidase (NA) of A/Tokyo/3/67 influenza virus (H2N2) were selected with a frequency of approximately 1 in 10 5 after a single passage of the virus in the presence of monoclonal antibody to the NA. Analysis of a panel of antigenic variants with N2 monoclonal antibodies provided evidence for at least three nonover-lapping antigenic areas on the neuraminidase molecule of A/Tokyo/3/67 and possibly four. Analysis of field strains showed that antigenic variation in the neuraminidase was evident even between influenza virus isolated in the first year following the emergence of a new pandemic strain. A/Japan/305/57 differed in at least seven epitopes from A/ Okuda/57 and A/RI/5 +/57. Antigenic drift occurred in each of the antigenic areas on the neuraminidase of human influenza virus from 1957 to 1979 with a gradual loss in reactivity with monoclonal antibodies to the early strains and acquisition of reactivity with antibodies to later strains. Only limited antigenic variation was detectable in the N2 neuraminidase for avian strains, over a similar time period; all of the avian N2 neuraminidases were closely related to the neuraminidase on A/Japan/305/57. Hemagglutination inhibition by monoclonal antibodies to the NA occurred in some but not all N2 viruses. These results suggest that the distribution of neuraminidase molecules may differ among viruses possessing N2 neuraminidase.