For the development of a universal infl uenza vaccine, a possible target is the relatively conserved M2 homotetramer. The concept is based on identifying alternative infl uenza antigens that are not as susceptible to antigenic shift and drift. Some degree of protection was induced in mice by priming with an M2 ectodomain peptide in adjuvant (29) . Studies that used the M2eA peptide conjugated to keyhole limpet hemocyanin and Neisseria meningitidis outer membrane protein illustrated good immune responses not only in mice but also in ferrets and rhesus monkeys (30) . In a recent study, 3 M2eA sequences, representing a range of epidemic strains and the (H5N1) strain, were fused to a proprietary hydrophobic protein domain. The resulting fusion proteins, formulated in liposomes, stimulated a protective response in mice challenged with subtypes H1N1, H5N1, H6N2, or H9N2 (31) . Previous studies have shown that when M2e is linked to hepatitis B virus core (HBc) particles, it becomes highly immunogenic, eliciting protective antibody response in mice (25) . Recently, a series of M2e-HBc constructs were made by increasing the copy number of M2e inserted at the N terminus from 1 to 3 per monomer. The best protection was seen when mice were vaccinated intranasally with these constructs combined with CTA1-DD, a cholera toxin A1-derived mucosal adjuvant (32) .