In vivo efficacy of a chitosan/IL-12 adjuvant system for protein-based vaccines.
Vaccines based on recombinant proteins require adjuvant systems in order to generate Th1-type immune responses. We have developed a vaccine adjuvant system using a viscous chitosan solution and interleukin (IL)-12, a Th1-inducing cytokine. The chitosan solution is designed to create a depot of antigen and IL-12 at a subcutaneous injection site. We measured the in vivo immune response of a vaccine containing 0.25, 1, or 4 μg murine IL-12 and 75 μg ovalbumin (OVA), formulated in a 1.5% chitosan glutamate solution. The chitosan/IL-12/OVA vaccine, in comparison to chitosan/OVA, IL-12/OVA, or OVA alone, elicited greater antigen-specific CD4(+) and CD8(+) T-cell responses, as determined by CD4(+) splenocyte proliferation, Th1 cytokine release, CD8(+) T-cell interferon-γ release, and MHC class I peptide pentamer staining. The combination of chitosan and IL-12 also enhanced IgG2a and IgG2b antibody responses to OVA. Co-formulation of chitosan and IL-12 thus promoted the generation of a Th1 immune response to a model protein vaccine.
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Michael J
MJ
Heffernan
David A
DA
Zaharoff
Jonathan K
JK
Fallon
Jeffrey
J
Schlom
John W
JW
Greiner
D000276:Adjuvants, Immunologic / Q000378:metabolism*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D048271:Chitosan / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011506:Proteins / Q000276:immunology*; D014612:Vaccines / Q000276:immunology*
D000276:Adjuvants, Immunologic; D011506:Proteins; D014612:Vaccines; D018664:Interleukin-12; D007371:Interferon-gamma; D048271:Chitosan