title: Effects of different adjuvants in the context of intramuscular and intranasal routes on humoral and cellular immune responses induced by detergent-split A/H3N2 influenza vaccines in mice.
abstract: Influenza A/H3N2 viruses have caused the most severe epidemics since 1968 despite current immunization programs with inactivated vaccines. We undertook a side-by-side preclinical evaluation of different adjuvants (Alum, AS03, and Protollin) and routes of administration (intramuscular [i.m.] and intranasal [i.n.]) for assessing their effect on the immunogenicity and cross-reactivity of inactivated split vaccines (A/H3N2/New York/55/2004). Humoral and T cell-mediated immune responses against the homologous virus and a heterologous drifted strain (A/H3N2/Wisconsin/67/2005) were measured in BALB/c mice at 2, 6, and 19 weeks postboost. The AS03- and Alum-adjuvanted i.m. vaccines induced at least an 8-fold increase over the nonadjuvanted vaccine in functional antibody titers against both the homotypic and heterotypic strains and low IgG2a and high IgG1 levels, suggesting a mixed Th1/Th2 response with a Th2 trend. The Protollin-adjuvanted i.n. vaccine induced the lowest IgG1/IgG2a ratio, which is indicative of a mixed Th1/Th2-type profile with a Th1 trend. This adjuvanted vaccine was the only vaccine to stimulate a mucosal IgA response. Whatever the timing after the boost, both hemagglutination inhibition (HAI) and microneutralization (MN) titers were higher with the AS03-adjuvanted i.m. vaccine than with the protollin-adjuvanted i.n. vaccine. Finally, the Alum-adjuvanted i.m. vaccine and the lower-dose Protollin-adjuvanted i.n. vaccine elicited significantly higher CD4(+) Th1 and Th2 responses and more gamma interferon (IFN-γ)-producing CD8(+) T cells than the nonadjuvanted vaccine. Our data indicate that the adjuvanted vaccines tested in this study can elicit stronger, more persistent, and broader immune responses against A/H3N2 strains than nonadjuvanted inactivated influenza vaccines.
authors.affiliation: Research Center in Infectious Diseases of the CHUL, CHUQ and Department of Microbiology and Immunology of Laval University, Quebec, Canada.
authors.forename: Mariana
authors.initials: M
authors.lastname: Baz
authors.forename: Mukesh
authors.initials: M
authors.lastname: Samant
authors.forename: Hakima
authors.initials: H
authors.lastname: Zekki
authors.forename: Pascale
authors.initials: P
authors.lastname: Tribout-Jover
authors.forename: Martin
authors.initials: M
authors.lastname: Plante
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Lanteigne
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Hamelin
authors.forename: Corey
authors.initials: C
authors.lastname: Mallett
authors.forename: Barbara
authors.initials: B
authors.lastname: Papadopoulou
authors.forename: Guy
authors.initials: G
authors.lastname: Boivin
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000281:Administration, Intranasal; D000534:Alum Compounds / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003546:Cysteine Endopeptidases / Q000008:administration & dosage / Q000276:immunology; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D006385:Hemagglutination Inhibition Tests; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000276:immunology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014611:Vaccination / Q000379:methods
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000914:Antibodies, Viral; D004338:Drug Combinations; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D008070:Lipopolysaccharides; C493785:Protollin; C041524:aluminum sulfate; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases