Serum and mucosal immune responses to an inactivated influenza virus vaccine induced by epidermal powder immunization

Both circulating and mucosal antibodies are considered important for protec tion against infection by influenza virus in humans and animals. However, c urrent inactivated vaccines administered by intramuscular injection using a syringe and needle elicit primarily circulating antibodies. In this study, we report that epidermal powder immunization (EPI) via a unique powder del ivery system elicits both serum and mucosal antibodies to an inactivated in fluenza virus vaccine. Serum antibody responses to influenza vaccine follow ing EPI were enhanced by codelivery of cholera toxin (CT), a synthetic olig odeoxynucleotide containing immunostimulatory CpG motifs (CpG DNA), or the combination of these two adjuvants. In addition, secretory immunoglobulin A (sIgA) antibodies were detected in the saliva and mucosal lavages of the s mall intestine, trachea, and vaginal tract, although the titers were much l ower than the IgG titers. The local origin of the sIgA antibodies was furth er shown by measuring antibodies released from cultured tracheal and small intestinal fragments and by detecting antigen-specific IgA-secreting cells in the lamina propria using ELISPOT assays. EPI with a single dose of influ enza vaccine containing CT or CT and CpG DNA conferred complete protection against lethal challenges with an influenza virus isolated 30 years ago, wh ereas a prime and boost immunizations were required for protection in the a bsence of an adjuvant. The ability to elicit augmented circulating antibody and mucosal antibody responses makes EPI a promising alternative to needle injection for administering vaccines against influenza and other diseases.