Focused antibody response to influenza linked to antigenic drift

The selective pressure that drives antigenic changes in influenza viruses is thought tooriginate from the human immune response. Here, we have characterized the B cellrepertoire from a previously vaccinated donor whose serum had reduced neutralizingactivity against the recently evolved clade 6B H1N1pdm09 viruses. While the response wasmarkedly polyclonal, 88% of clones failed to recognize clade 6B viruses; however, theability to neutralize A/USSR/90/1977 influenza, to which the donor would have been exposedin childhood, was retained. In vitro selection of virus variants with representativemonoclonal antibodies revealed that a single amino acid replacement at residue K163 in theSa antigenic site, which is characteristic of the clade 6B viruses, was responsible forresistance to neutralization by multiple monoclonal antibodies and the donor serum. TheK163 residue lies in a part of a conserved surface that is common to the hemagglutinins ofthe 1977 and 2009 H1N1 viruses. Vaccination with the 2009 hemagglutinin induced anantibody response tightly focused on this common surface that is capable of selectingcurrent antigenic drift variants in H1N1pdm09 influenza viruses. Moreover, amino acidreplacement at K163 was not highlighted by standard ferret antisera. Human monoclonalantibodies may be a useful adjunct to ferret antisera for detecting antigenic drift ininfluenza viruses.