Evaluation of a liposome-supplemented intranasal influenza subunit vaccinein a murine model system: Induction of systemic and local mucosal immunity

This study reports on the mucosal immunoadjuvant activity of liposomes in a n experimental influenza subunit vaccine administered intranasally (i.n.) t o mice. Antibody responses induced by the i.n. liposomal vaccine were compa red to those induced by an influenza infection or by subcutaneous (s.c.) in jection of subunit antigen alone, the conventional route of human flu vacci nation. Negatively charged liposomes, but not positively charged or zwitter ionic liposomes, coadministered i.n. with influenza subunit antigen, signif icantly stimulated systemic Ige levels and local antibody responses in pulm onary secretions, relative to the responses upon i.n. administration of sub unit antigen alone. I.n. immunization with liposome-supplemented subunit an tigen as well as s.c. immunization with subunit antigen alone or infection induced high levels of IgG antibodies in serum and pulmonary secretions, wi th a preferential induction of IgG1 upon immunization and IgG2a upon infect ion. Both i.n. immunization with liposome-supplemented antigen and infectio n, but not s.c. immunization with subunit antigen alone, induced local secr etion of S-IgA. At the same time, both IgA- and IgG-secreting cells appeare d in the lungs and lung-associated lymph nodes, suggestive of local antibod y production. In conclusion, the liposomal adjuvant system, combined with a mucosal administration protocol, provides a promising strategy for inducti on of both systemic and local antibody responses against influenza virus.