Nasal or intramuscular immunization of mice with influenza subunit antigenand the B subunit of Escherichia coli heat-labile toxin induces IgA- or IgG-mediated protective mucosal immunity

Local mucosal IgA antibodies play a central role in protection of the respi ratory tract against influenza virus infection. Therefore, new-generation i nfluenza vaccines should aim at stimulating not only systemic, but also loc al antibody responses. Previously, we demonstrated that the recombinant B s ubunit of the Escherichia coli heat-labile toxin (LTB) is a potent adjuvant towards nasally administered influenza subunit antigen. Here, we investiga ted the protection conferred by LTB-supplemented influenza subunit antigen given intranasally (i.n.) or intramuscularly (i.m.) to mice. Both i.n. and i.m. immunization with subunit antigen and LTB completely protected the ani mals against viral infection. Protection upon i.n. immunization was associa ted with the induction of antigen-specific serum IgG and mucosal IgA, where as protection upon i.m. immunization correlated with strong serum and mucos al IgG, but not IgA responses. We conclude that LTB-supplemented influenza subunit antigen, given either i.n. or i.m, induces protective antibody-medi ated mucosal immunity and thus represents a promising novel flu vaccine can didate. (C) 2001 Elsevier Science Ltd. All rights reserved.