title: IL-12 enhances antibody responses to T-independent polysaccharide vaccines in the absence of T and NK cells.
abstract: Polysaccharide vaccines to encapsulated bacteria such as Neisseria meningitidis and Streptococcus pneumoniae are weakly immunogenic due to their T-independent (TI) nature. Even when converted to T-dependent forms through conjugation to foreign proteins, polysaccharides induce responses that are deficient in many respects, such as induction of murine IgG2a Ab, the isotype that mediates optimal complement fixation and opsonization. We now show that IL-12 treatment of mice induces significantly increased levels of IgG2a Ab to the model TI-2 Ag, DNP-Ficoll, and to vaccines composed of polysaccharides from pneumococci and meningococci. Use of immunodeficient mice lacking T cells and/or NK cells demonstrated that such cells were not responsible for the observed Ab enhancement. Furthermore, the use of IFN-gamma knockout mice showed that stimulation of TI-2 Ab responses by IL-12 was only partially dependent on IFN-gamma. The ability of IL-12 to dramatically enhance TI Ab responses suggests that IL-12 will be useful as a powerful vaccine adjuvant to induce protective immune responses against encapsulated pathogens.
authors.affiliation: Department of Microbiology and Immunology, Medical College of Ohio, Toledo 43614-5806, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Buchanan
authors.forename: B P
authors.initials: BP
authors.lastname: Arulanandam
authors.forename: D W
authors.initials: DW
authors.lastname: Metzger
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D000917:Antibody Formation; D000955:Antigens, T-Independent / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D004140:Dinitrophenols / Q000276:immunology; D005362:Ficoll / Q000031:analogs & derivatives / Q000276:immunology; D006241:Haptens / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000502:physiology; D018664:Interleukin-12 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009345:Neisseria meningitidis / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000955:Antigens, T-Independent; D001428:Bacterial Vaccines; C031007:DNP-Ficoll; D004140:Dinitrophenols; D006241:Haptens; D007074:Immunoglobulin G; D016898:Interferon-alpha; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; C045521:dinitrophenol-ovalbumin; D018664:Interleukin-12; D005362:Ficoll; D007371:Interferon-gamma; D010047:Ovalbumin