Current influenza vaccines provide hemagglutinin strain-specific protection， but rarely provide cross-protection against divergent strains. It is， therefore， particularly important to develop a universal vaccine against conserved proteins or conserved regions of the virus. In this study， we used N-terminal extracellular region of the influenza virus M2 protein (M2e) as the target antigen and constructed two optimized M2e DNA vaccines (p-tPA-p3M2e and p-p3M2e) with increased antigenic epitope density and enhanced antigen secretion. Both vaccines induced high M2e-specific humoral and cellular immune responses in the vaccinated mice. These two vaccines also conferred protection against a lethal infection o... More
Current influenza vaccines provide hemagglutinin strain-specific protection， but rarely provide cross-protection against divergent strains. It is， therefore， particularly important to develop a universal vaccine against conserved proteins or conserved regions of the virus. In this study， we used N-terminal extracellular region of the influenza virus M2 protein (M2e) as the target antigen and constructed two optimized M2e DNA vaccines (p-tPA-p3M2e and p-p3M2e) with increased antigenic epitope density and enhanced antigen secretion. Both vaccines induced high M2e-specific humoral and cellular immune responses in the vaccinated mice. These two vaccines also conferred protection against a lethal infection of homo-subtypic H1N1 virus， with p-tPA-p3M2e being the most effective. In addition， p-tPA-p3M2e also showed cross-protection against different subtypes of the influenza virus (H9N2， H6N6， and H10N8) at varying rates (80%， 40%， and 20%， respectively). After passive immunization， M2e DNA vaccine-induced antibodies in the sera provided complete protection against homologous virus challenge. An analysis of the mechanism underlying this immunization-mediated protection indicates that M2e-specific IgG and T-cell immune responses may play critical roles in the prevention of infection and viral clearance. Taken together， our results indicate that this optimized M2e DNA vaccine is a promising candidate for the development of a universal， broad-spectrum influenza virus vaccine.
