Synthetic vaccines utilize specific antigenic epitopes in order to elicit a protective immune response. In this work we examined the immunogenicity of chimeric proteins expressing influenza epitopes and their ability, as single products or in various combinations, to protect mice from viral challenge. Oligonucleotides coding for three epitopes (HA91-108, NP55-69 and NP147-158) stimulating B cells, T helper cells and cytotoxic T lymphocytes (CTLs), respectively, were individually inserted into the flagellin gene of a Salmonella vaccine strain. Immunization of mice with the resultant hybrid flagella resulted in a specific humoral or cellular response. The protective efficacy of the chimeric flagella was evaluated by intranasal immunization of mice, without any adjuvant, and subsequent challenge with infectious virus. The construct containing the B-cell epitope by itself led to partial protection. However, the addition of the two T-cell epitopes augmented the protection in a significant manner. The protective immunity conferred by this combined vaccine, comprising the three epitopes, persisted for at least 7 months after the last boost, and was effective against several influenza A strains. Furthermore, this vaccine fully protected mice from a lethal challenge, and enhanced their recovery process. Our results indicate that stimulation of the different arms of the immune system is required for effective anti-influenza response, and demonstrate the applicability of such synthetic recombinant approach for preparing a broad spectrum influenza vaccine.