title: Intranasal delivery of influenza rNP adjuvanted with c-di-AMP induces strong humoral and cellular immune responses and provides protection against virus challenge.
abstract: There is a critical need for new influenza vaccines able to protect against constantly emerging divergent virus strains. This will be sustained by the induction of vigorous cellular responses and humoral immunity capable of acting at the portal of entry of this pathogen. In this study we evaluate the protective efficacy of intranasal vaccination with recombinant influenza nucleoprotein (rNP) co-administrated with bis-(3',5')-cyclic dimeric adenosine monophosphate (c-di-AMP) as adjuvant. Immunization of BALB/c mice with two doses of the formulation stimulates high titers of NP-specific IgG in serum and secretory IgA at mucosal sites. This formulation also promotes a strong Th1 response characterized by high secretion of INF-γ and IL-2. The immune response elicited promotes efficient protection against virus challenge. These results suggest that c-di-AMP is a potent mucosal adjuvant which may significantly contribute towards the development of innovative mucosal vaccines against influenza.
authors.affiliation: Laboratory of Virology, Institute of Experimental Medicine and Biology of Cuyo (IMBECU-CCT, CONICET), Mendoza, Argentina; Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Maria Victoria
authors.initials: MV
authors.lastname: Sanchez
authors.affiliation: Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ebensen
authors.affiliation: Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Schulze
authors.affiliation: Laboratory of Virology, Institute of Experimental Medicine and Biology of Cuyo (IMBECU-CCT, CONICET), Mendoza, Argentina.
authors.forename: Diego
authors.initials: D
authors.lastname: Cargnelutti
authors.affiliation: Boehringer Ingelheim Veterinary Research Center GmbH & Co. KG, Hannover, Germany.
authors.forename: Paulina
authors.initials: P
authors.lastname: Blazejewska
authors.affiliation: Laboratory of Virology, Institute of Experimental Medicine and Biology of Cuyo (IMBECU-CCT, CONICET), Mendoza, Argentina.
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Scodeller
authors.affiliation: Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Guzmán
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D005260:Female; D007111:Immunity, Cellular / Q000276:immunology*; D056724:Immunity, Humoral / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination / Q000379:methods
chemical_list: D007252:Influenza Vaccines