ANALYSIS OF ANTIGENIC DRIFT IN RECENTLY ISOLATED INFLUENZA-A (H1N1) VIRUSES USING MONOCLONAL ANTIBODY PREPARATIONS

Monoclonal antibodies to the hemagglutinin (HA) and neuraminidase (NA) of A/USSR/ 90/77(HlN1) were prepared and used to study antigenic drift in the H1N1 subtype of influenza viruses. The results obtained with five different monoclones to each molecule were compared with the results obtained with postinfection ferret sera. Monoclonal antibodies and postinfection ferret sera detected antigenic drift in the hemagglutinin and neuraminidase molecules of H1N1 viruses and monoclonal antibodies showed that the A/USSR/90/77, A/ Roma/1/49, and A/Fort Warren/1/50 viruses were identical at five sites on both the hemagglutinin and neuraminidase molecules. To further evaluate monoclonal antibodies, they were used in hemagglutination inhibition tests with recently isolated influenza A(HlNl) viruses, including some shown in tests with postinfection ferret sera to have undergone antigenic drift. Three patterns of reactivity with the monoclonal antibodies were detected with the variants: two variants differed at two of the five sites identified by the monoclonal antibodies and a third variant differed at only one of the five sites. Two of these variant groupings had not been distinguished from each other in HI tests with ferret sera, whereas ferret sera were capable of distinguishing between two groups of variants that had similar reaction patterns with the five monoclonal antibody preparations. Monoclonal antibodies failed to detect antigenic drift in the NA molecules of the recent isolates of H1N1 influenza viruses, suggesting that antigenic changes occur less frequently in this molecule. The observation that antigenic differences could be detected between the recent variants with such a small panel of monoclonal antibodies (less than 10% of the number obtained to the HA of A/PR/8/34) suggests that monoclonal antibodies may provide an exquisitely sensitive method for antigenic mapping of influenza viruses. © 1979.