Seasonal influenza viruses continue to infect humans yearly shaping a baseline level of immunity. Recently, highly pathogenic avian influenza H5N1 clade 2.3.4.4b virus infected different mammalian species including spillover to humans. In this thesis we aim to quantify the baseline level of immunity in the general population and to identify individuals that are potentially more at risk of developing a severe infection during a potential H5N1 pandemic.

First, we detected H5N1 cross-neutralizing antibodies in a healthy adult population in Geneva and suggested a possible mechanism of cross-neutralization mediated by HA reactive antibodies that inhibit NA enzymatic activity during viral release and spreading.

We then explored whether previous seasonal influenza vaccination influenced H5N1 cross-neutralizing antibody titers, to assess if existing vaccines could serve as a preventive tool in the event of an H5N1 pandemic while an H5N1-specific vaccine is being developed.

In conclusion, we showed that H5N1 unexposed healthy adults have different levels of H5N1 cross-neutralizing antibody titers at baseline, but AS03-adjuvanted influenza vaccination can overcome these immune imprinting differences.