Mucosal adjuvants for influenza virus-like particle vaccine.

To find an effective mucosal adjuvant for influenza virus-like particles (VLPs), we compared the effects of known adjuvants Alum, CpG DNA, monophosphoryl lipid A (MPL), poly IC, gardiquimod, and cholera toxin (CT). Mice that were intranasally immunized with Alum, CpG, MPL, and CT adjuvanted VLPs showed higher levels of antibodies in both sera and mucosa. Hemagglutination inhibition and virus neutralizing activities were enhanced in groups adjuvanted with Alum, MPL, or CT. Influenza virus specific long-lived cells secreting IgG and IgA antibodies were found at high levels both in bone marrow and spleen in the Alum, CpG and CT adjuvanted groups. A similar level of protection was observed among different adjuvanted groups, except the CT adjuvant that showed a higher efficacy in lowering lung viral loads after challenge. Alum and CT adjuvants differentially increased influenza VLP-mediated activation of dendritic cells and splenocytes in vitro, supporting the in vivo pattern of antibody isotypes and cytokine production. These results suggest that Alum, MPL, or CpG adjuvants, which have been tested clinically, can be developed as an effective mucosal adjuvant for influenza VLP vaccines.