title: Cationic lipid/DNA complexes (JVRS-100) combined with influenza vaccine (Fluzone) increases antibody response, cellular immunity, and antigenically drifted protection.
abstract: Safe and effective adjuvants for influenza vaccines that could increase both the levels of neutralizing antibody, including against drifted viral subtypes, and T-cell immunity would be a major advance in vaccine design. The JVRS-100 adjuvant, consisting of DOTIM/cholesterol cationic liposome-DNA complexes, is particularly promising for vaccines that require induction of high levels of antibody and T-cell immunity, including CD8(+) cytotoxic T lymphocytes (CTL). Inclusion of protein antigens with JVRS-100 results in the induction of enhanced humoral and cell-mediated (i.e., CD4(+) and CD8(+) T cells) immune responses. The JVRS-100 adjuvant combined with a split trivalent influenza vaccine (Fluzone-sanofi pasteur) elicited increased antibody and T-cell responses in mice and non-human primates compared to vaccination with Fluzone alone. Mice vaccinated with JVRS-100-Fluzone and challenged with antigenically drifted strains of H1N1 (PR/8/34) and influenza B (B/Lee/40) viruses had higher grade protection, as measured by attenuation of weight loss and increased survival, compared to recipients of unadjuvanted vaccine. The results indicate that the JVRS-100 adjuvant substantially increases immunogenicity and protection from drifted-strain challenge using an existing influenza vaccine.
authors.affiliation: Juvaris BioTherapeutics, Inc, Burlingame, CA 94010, USA.
authors.forename: Marla
authors.initials: M
authors.lastname: Lay
authors.forename: Bernadette
authors.initials: B
authors.lastname: Callejo
authors.forename: Stella
authors.initials: S
authors.lastname: Chang
authors.forename: David K
authors.initials: DK
authors.lastname: Hong
authors.forename: David B
authors.initials: DB
authors.lastname: Lewis
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Carroll
authors.forename: Shannon
authors.initials: S
authors.lastname: Matzinger
authors.forename: Linda
authors.initials: L
authors.lastname: Fritts
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Miller
authors.forename: John F
authors.initials: JF
authors.lastname: Warner
authors.forename: Lily
authors.initials: L
authors.lastname: Liang
authors.forename: Jeffery
authors.initials: J
authors.lastname: Fairman
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D001835:Body Weight; D004247:DNA / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D009981:Influenza B virus / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D008081:Liposomes / Q000008:administration & dosage / Q000494:pharmacology*; D008253:Macaca mulatta; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*; D022223:Vaccines, Subunit / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D008081:Liposomes; D022223:Vaccines, Subunit; D004247:DNA