Antigenic drift in influenza A/USSR/90/77(H1N1) variants selected in Vitro with monoclonal antibodies

Abstract

Variants of A/USSR/90/77(H1N1) virus were selected in vitro by breakthrough neutralization with monoclonal antibodies, at a frequency consistent with them arising by single-step point mutations. When examined by hemagglutination-inhibition tests with postinfection ferret sera, all those variants with a change in the epitope recognized by antibody 264 exhibited significant antigenic drift away from A/USSR/90/77, whereas no variants lacking a change in the epitope recognized by this antibody differed from A/USSR/90/77 when tested with the heterogeneous sera. One of the in vitro variants had acquired a distinctive specificity with ferret sera similar to that of a previously described sporadically detected, natural variant, A/Lackland/3/78, that exhibits reciprocal antigenic drift from A/USSR/90/77. Another variant was quite similar to the epidemic strain A/Brazil/11/78 in its ferret serum reaction pattern, exhibiting modest asymmetric antigenic drift from A/USSR/90/77. The in vitro variants were not, however, identical to natural variants in reaction patterns with both monoclonal antibodies and ferret sera. Nevertheless, the findings support the possibility for significant antigenic variation of A/USSR/90/77 influenza virus to occur by means of a point mutation at a critical locus in the determinant recognized by monoclonal antibody 264, and suggest that some natural variants may have arisen by point mutations in this determinant.