Avian infl uenza A viruses of the H5N1 subtype are currently causing widespread infections in bird populations. Numerous instances of transmission to humans have been recently reported in Asia and Africa, with the infection resulting in severe disease or death (>50% fatality rate). Hence, the aim of the present study was to evaluate the immune cross-reactivity between human and avian infl uenza (H5N1) strains in healthy donors recently vaccinated for seasonal infl uenza A (H1N1/H3N2). Our data indicate that infl uenza vaccination may boost cross-subtype immunity against infl uenza (H5N1), involving cellular or humoral responses or both.