title: Preclinical evaluation of Vaxfectin-adjuvanted Vero cell-derived seasonal split and pandemic whole virus influenza vaccines.
abstract: Increasing the potency and supply of seasonal and pandemic influenza vaccines remains an important unmet medical need which may be effectively accomplished with adjuvanted egg- or cell culture-derived vaccines. Vaxfectin, a cationic lipid-based adjuvant with a favorable safety profile in phase 1 plasmid DNA vaccines trials, was tested in combination with seasonal split, trivalent and pandemic whole virus, monovalent influenza vaccines produced in Vero cell cultures. Comparison of hemagglutination inhibition (HI) antibody titers in Vaxfectin-adjuvanted to nonadjuvanted vaccinated mice and guinea pigs revealed 3- to 20-fold increases in antibody titers against each of the trivalent influenza virus vaccine strains and 2- to 8-fold increases in antibody titers against the monovalent H5N1 influenza virus vaccine strain. With the vaccine doses tested, comparable antibody responses were induced with formulations that were freshly prepared or refrigerated at conventional 2-8°C storage conditions for up to 6 mo. Comparison of T-cell frequencies measured by interferon-gamma ELISPOT assay between groups revealed increases of between 2- to 10-fold for each of the adjuvanted trivalent strains and up to 22-fold higher with monovalent H5N1 strain. Both trivalent and monovalent vaccines were easy to formulate with Vaxfectin by simple mixing. These preclinical data support further testing of Vaxfectin-adjuvanted Vero cell culture vaccines toward clinical studies designed to assess safety and immunogenicity of these vaccines in humans.
authors.affiliation: Vical Incorporated; San Diego, CA USA.
authors.forename: Larry R
authors.initials: LR
authors.lastname: Smith
authors.forename: Walter
authors.initials: W
authors.lastname: Wodal
authors.forename: Brian A
authors.initials: BA
authors.lastname: Crowe
authors.forename: Astrid
authors.initials: A
authors.lastname: Kerschbaum
authors.forename: Peter
authors.initials: P
authors.lastname: Bruehl
authors.forename: Michael G
authors.initials: MG
authors.lastname: Schwendinger
authors.forename: Helga
authors.initials: H
authors.lastname: Savidis-Dacho
authors.forename: Sean M
authors.initials: SM
authors.lastname: Sullivan
authors.forename: Mark
authors.initials: M
authors.lastname: Shlapobersky
authors.forename: Jukka
authors.initials: J
authors.lastname: Hartikka
authors.forename: Alain
authors.initials: A
authors.lastname: Rolland
authors.forename: P Noel
authors.initials: PN
authors.lastname: Barrett
authors.forename: Otfried
authors.initials: O
authors.lastname: Kistner
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D006168:Guinea Pigs; D006385:Hemagglutination Inhibition Tests; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010714:Phosphatidylethanolamines / Q000008:administration & dosage*; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D010714:Phosphatidylethanolamines; D022223:Vaccines, Subunit; C460866:vaxfectin; D007371:Interferon-gamma
keywords: H5N1; Vaxfectin®; Vero cell culture; adjuvant; cationic liposomes; influenza vaccine