IL-12 enhances vaccine-induced immunity to schistosomes by augmenting both humoral and cell-mediated immune responses against the parasite.
The production of Th1-type cytokines is associated with strong cell-mediated immunity, while Th2-type cytokines typically dominate humoral immune responses. In mice vaccinated a single time with attenuated cercariae of Schistosoma mansoni, the protection induced is associated with Th1 cytokine-dependent, cell-mediated immunity. In contrast, mice vaccinated multiple times display a more Th2-type dominant cytokine response and develop Ab-dependent resistance. We have previously shown that IL-12 enhances cell-mediated immunity in singly vaccinated mice. In the present study, we asked what effects administering IL-12 as an adjuvant would have on the development of a protective humoral response in multiply immunized animals. We found that multiply immunized/IL-12-treated mice displayed a marked increase in resistance to challenge infection, with some animals demonstrating complete protection. The IL-12-vaccinated mice developed strongly polarized Th1 responses but, importantly, also showed significant increases in parasite-specific Ab and, in particular, IgG2a, IgG2b, and IgG1 isotypes. Passive transfer demonstrated an enhanced ability of serum from these animals to protect naive recipients. In addition, animals vaccinated in the presence of IL-12 also developed macrophages with increased nitric oxide-dependent killing activity against the parasites. Together, these data demonstrate that IL-12, initially described as an adjuvant for cell-mediated immunity, may be used to simultaneously to promote both humoral and cell-mediated protective responses against infection.
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. tw12b@nih.gov
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Wynn
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Reynolds
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James
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Cheever
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Caspar
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Hieny
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Jankovic
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Strand
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Sher
D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis* / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects; D018664:Interleukin-12 / Q000494:pharmacology*; D007814:Larva; D008168:Lung / Q000469:parasitology / Q000473:pathology; D008262:Macrophage Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D012550:Schistosoma mansoni / Q000254:growth & development / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014611:Vaccination
D000909:Antibodies, Helminth; D016207:Cytokines; D018664:Interleukin-12; D009569:Nitric Oxide