Cationic lipid/DNA complexes (JVRS-100) combined with influenza vaccine (Fluzone) increases antibody response, cellular immunity, and antigenically drifted protection.
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.
Lay
Marla
M
Juvaris BioTherapeutics, Inc, Burlingame, CA 94010, USA.
Callejo
Bernadette
B
Chang
Stella
S
Hong
David K
DK
Lewis
David B
DB
Carroll
Timothy D
TD
Matzinger
Shannon
S
Fritts
Linda
L
Miller
Christopher J
CJ
Warner
John F
JF
Liang
Lily
L
Fairman
Jeffery
J
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*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D008081:Liposomes; D022223:Vaccines, Subunit; D004247:DNA