Subsequent vaccination with antigenically very distinct influenza viruses of a given HA subtype (heterovariant vaccination) seems to be very effective in stimulating memory B cells that recognize conserved epitopes in the viral haemagglutinin (HA) and that produce broadly-reactive antibodies. Using this vaccination strategy we aim at a) protecting swine against European and North American H3N2 swine influenza viruses and b) protecting humans against drift variants of human H3N2 viruses and against potentially pandemic H3N2 viruses from swine. The following questions will be studied for H3N2 viruses of swine and humans:

• Will subsequent vaccination with inactivated H3N2 viruses belonging to distinct antigenic clusters result in a broader antibody response and protection?
• What is the effect of the genetic relationship between the viruses and the sequence of administration? Many different protocols will be compared for the human viruses.
• What role do cross-reactive antibody producing (B) cells play, as well as T helper cells?