Safety and immunogenicity of adjuvanted and unadjuvanted subunit influenzavaccines administered intranasally to healthy adults

Antigen-specific mucosal immunity is thought to be important for protection against influenza virus infection. Currently licensed parenteral influenza vaccines stimulate the production of serum antibodies, but are poor induce rs of mucosal immunity. The adjuvant MF59 has been shown to enhance the hum oral immune response to parenteral influenza vaccine in humans and the muco sal immune response to intranasally-administered influenza Vaccine in mice. We conducted an open-label safety study followed by an observer-blind, ran domized trial comparing the immune response to intranasally-administered su bunit influenza Vaccine adjuvanted with MF59, unadjuvanted subunit influenz a vaccine, and placebo. Adverse reactions did not occur significantly more frequently in vaccinees than placebo recipients. Of 31 subjects receiving 2 doses of MF59-adjuvanted influenza vaccine, 19 (61%), 8 (26%), and 11 (35% ) developed a mucosal IgA response to influenza A/H1N1, A/H3N2, and B, resp ectively. The percentage of subjects with a serum antibody response was sli ghtly lower. The immune responses to adjuvanted vaccine were not significan tly different from those to unadjuvanted vaccine. Both vaccines gave more f requent responses than seen in placebo recipients, indicating the potential of intranasal inactivated vaccines to stimulate local IgA responses. (C) 2 000 Elsevier Science Ltd. All rights reserved.