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

• Published in: Vaccine 2001-04, Vol.19 (20), p.2898-2907
• Main Authors: Haan, Lolke de, Verweij, Willem R, Holtrop, Marijke, Brands, Ruud, van Scharrenburg, Guus J.M, Palache, Abraham M, Agsteribbe, Etienne, Wilschut, Jan
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Administration, Intranasal; Animals; Antibodies, Viral - immunology; Bacterial Toxins - administration & dosage; Biological and medical sciences; Enterotoxins - administration & dosage; Escherichia coli; Escherichia coli Proteins; Female; Fundamental and applied biological sciences. Psychology; heat-labile toxin; Immunization; Immunoglobulin A, Secretory - immunology; Immunoglobulin G - immunology; Influenza Vaccines - administration & dosage; Influenza Vaccines - immunology; influenza virus; Injections, Intramuscular; Lung - virology; Mice; Mice, Inbred BALB C; Microbiology; Nasal Mucosa - virology; Protein Subunits; Rats; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Virology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/S0264-410X(00)00556-9

Local mucosal IgA antibodies play a central role in protection of the respiratory tract against influenza virus infection. Therefore, new-generation influenza vaccines should aim at stimulating not only systemic, but also local antibody responses. Previously, we demonstrated that the recombinant B subunit of the Escherichia coli heat-labile toxin (LTB) is a potent adjuvant towards nasally administered influenza subunit antigen. Here, we investigated 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 animals against viral infection. Protection upon i.n. immunization was associated with the induction of antigen-specific serum IgG and mucosal IgA, whereas protection upon i.m. immunization correlated with strong serum and mucosal IgG, but not IgA responses. We conclude that LTB-supplemented influenza subunit antigen, given either i.n. or i.m, induces protective antibody-mediated mucosal immunity and thus represents a promising novel flu vaccine candidate.