title: Combination adjuvants for the induction of potent, long-lasting antibody and T-cell responses to influenza vaccine in mice.
abstract: Influenza is controlled by protective titres of neutralizing antibodies, induced with the help of CD4 T-cells, and by antiviral T-cell effector function. Adjuvants are essential for the efficient vaccination of a naïve population against avian influenza. We evaluated a range of adjuvants for their ability to enhance, in naïve mice, protective hemagglutination inhibition (HI) titres, which represent the generally accepted correlate of protection, virus-neutralizing titres and T-cell responses to a new generation influenza vaccine produced in cell culture. The selected adjuvants include alum, calcium phosphate (CAP), MF59, the delivery system poly-(lactide co-glycolide) (PLG) and the immune potentiator CpG. MF59 was clearly the most potent single adjuvant and induced significantly enhanced, long-lasting HI and neutralizing titres and T-cell responses in comparison to all alternatives. The combination of alum, MF59, CAP or PLG with CpG generally induced slightly more potent titres. The addition of CpG to MF59 also induced a more potent Th1 cellular immune response, represented by higher IgG2a titres and the induction of a strongly enhanced IFN-gamma response in splenocytes from immunized mice. These observations have significant implications for the development of new and improved flu vaccines against pandemic and inter-pandemic influenza virus strains.
authors.affiliation: Novartis Vaccines, Via Fiorentina 1, Siena, Italy. andreas.wack@novartis.com
authors.forename: Andreas
authors.initials: A
authors.lastname: Wack
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Baudner
authors.forename: Anne K
authors.initials: AK
authors.lastname: Hilbert
authors.forename: Ilaria
authors.initials: I
authors.lastname: Manini
authors.forename: Sandra
authors.initials: S
authors.lastname: Nuti
authors.forename: Simona
authors.initials: S
authors.lastname: Tavarini
authors.forename: Hanno
authors.initials: H
authors.lastname: Scheffczik
authors.forename: Mildred
authors.initials: M
authors.lastname: Ugozzoli
authors.forename: Manmohan
authors.initials: M
authors.lastname: Singh
authors.forename: Jina
authors.initials: J
authors.lastname: Kazzaz
authors.forename: Emanuele
authors.initials: E
authors.lastname: Montomoli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Del Giudice
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.forename: Derek T
authors.initials: DT
authors.lastname: O'Hagan
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000918:Antibody Specificity; D002130:Calcium Phosphates / Q000276:immunology; D002460:Cell Line; D004655:Emulsions; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D009981:Influenza B virus / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000096:biosynthesis; D019344:Lactic Acid / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D009975:Orthomyxoviridae / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011136:Polysorbates; D013154:Spleen / Q000276:immunology; D013185:Squalene / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D002130:Calcium Phosphates; D004655:Emulsions; D007074:Immunoglobulin G; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011108:Polymers; D011136:Polysorbates; D022223:Vaccines, Subunit; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D013185:Squalene; D007371:Interferon-gamma; C020243:calcium phosphate