The use of interleukin-12 as a vaccine adjuvant for polysaccharide antigens

The vaccines currently available for Streptococcus pneumoniae and Neisseria meningitidis are composed of polysaccharide antigens that do not elicit T cell help and are consequently poorly immunogenic. In the absence of T cells, the antibody responses lack isotype switching, affinity maturation and memory. Conjugate vaccines, which convert a T-independent type 2 response to a more effective T-dependent response, have now been developed for both pathogens. It was previously shown that interleukin-12 enhances antigen-specific antibody responses and induces isotype switching to IgG2a, the murine isotype that is most efficient in mediating complement fixation and opsonophagocytosis. In the present study, I investigated the influence of interleukin-12 on antibody responses specific for pneumococcal and meningococcal polysaccharides and polysaccharide conjugate vaccines. In all cases, vaccinated mice treated with interleukin-12 had enhanced antigen-specific IgG2a levels. In addition, the use of interferon-gamma knockout mice demonstrated that interleukin-12 enhancement of antibody levels to both types of vaccines was interferon-gamma-dependent and -independent. Passive transfer of immune serum demonstrated that interleukin-12 treatment at the time of vaccination did not increase the protective immunity of the polysaccharide vaccines, but resulted in a delay in death and/or complete protection against bacterial challenge when administered with the conjugate vaccines. Taken together, this study demonstrates that interleukin-12 treatment at the time of vaccination enhances antigen-specific antibody levels to polysaccharide and polysaccharide conjugate vaccines and that the mechanism of enhancement is both interferon-gamma-dependent and -independent. In addition, interleukin-12 enhances the protective efficacy of conjugate vaccines further establishing that interleukin-12 may be a useful vaccine adjuvant.