Intranasal influenza vaccination using a new synthetic mucosal adjuvant SF‐10: induction of potent local and systemic immunity with balanced Th1 and Th2 responses

Background We found previously that bovine pulmonary Surfacten ® used in newborns with acute respiratory distress syndrome is a safe and efficacious antigen vehicle for intranasal vaccination. Objectives The objective of this study was to industrially produce a synthetic adjuvant mimicking Surfacten ® for clinical use without risk of bovine spongiform encephalopathy. Methods We selected three S urfacten lipids and surfactant protein ( SP )‐C as essential constituents for adjuvanticity. For replacement of the hydrophobic SP ‐C, we synthesized SP ‐related peptides and analyzed their adjuvanticity. We evaluated lyophilization to replace sonication for the binding of influenza virus hemagglutinin ( HA ) to the synthetic adjuvant. We also added a carboxy vinyl polymer ( CVP ) to the synthetic adjuvant and named the mixture as SF‐10 adjuvant. HA combined with SF‐10 was administered intranasally to mice, and induction of nasal‐wash HA ‐specific secretory IgA (s‐IgA) and serum IgG with Th1‐/Th2‐type cytokine responses in nasal cavity and virus challenge test were assessed. Results and Conclusions Intranasal immunization with HA–SF–10 induced significantly higher levels of anti‐ HA ‐specific nasal‐wash s‐ I gA and serum I gG than those induced by HA ‐poly(I:C), a reported potent mucosal vaccine, and provided highly efficient protection against lethal doses of virus challenge in mice. Anti‐ HA ‐specific serum I gG levels induced by HA–SF–10 were almost equivalent to those induced by subcutaneous immunization of HA twice. Intranasal administration of HA–SF–10 induced balanced anti‐ HA ‐specific I gG1 and I gG2a in sera and IFN ‐γ‐ and IL ‐4‐producing lymphocytes in nasal cavity without any induction of anti‐ HA I gE. The results suggest that HA–SF–10 is a promising nasal influenza vaccine and that SF ‐10 can be supplied in large quantities commercially.