[PubMed] [Google Scholar] 52

[PubMed] [Google Scholar] 52. the S3 antigen acknowledgement profile in each species. Isotyping of specific antibodies in S3- plus IL-12-vaccinated mice prior to challenge infection revealed a moderate elevation in immunoglobulin G1 (IgG1) responses, strongly enhanced IgG2a and IgG2b responses, as well as diminished total serum IgE responses compared to those in mice given S3 only. In vaccinated rats, IL-12 profoundly suppressed specific IgG1 and enhanced IgG2b responses but did not affect IgG2a responses. S3- plus IL-12-vaccinated rats also produced Saikosaponin B less total IgE upon challenge contamination. Enumeration of worm burdens revealed that vaccination with S3 plus IL-12 conferred 50% protection from cercarial challenge to rats, whereas rats given S3 only were not protected; mice were not guarded by S3 vaccination regardless of IL-12 Saikosaponin B coadministration. The protection observed in S3- plus IL-12-vaccinated rats could not be transferred with serum, suggesting participation of an activated cellular component in the expression of immunity. Immune responses to schistosome infections, as in several other models of infectious disease, have been Akt1 shown to be profoundly affected by certain subpopulations of T-helper (Th) cells, which exert a major influence around the development of protective responses in animal models (examined in recommendations 41 and 47). In the murine model of irradiated cercarial vaccination, immunity generated by a single vaccine dose is largely dependent on CD4+ T cells (22, 46, 56) and requires the T-helper type 1 (Th1)-associated cytokine gamma interferon (IFN-) (48, 50). Immunity can be augmented in this model by the coadministration of interleukin-12 (IL-12) (60, 61), a cytokine which has been shown to be a potent inducer of IFN- in vivo (15, 44). IL-12 has also been shown to induce Th1-associated immune responses and to confer protection to mice vaccinated with soluble lung-stage antigens (39). Although much of the research including IL-12 has focused on its role in promoting cell-mediated immune responses (5, 54, 58), the cytokine has been shown to bind to certain populations of B cells (57) and to Saikosaponin B function as a modest B-cell growth factor, acting in synergy with IL-2 to promote immunoglobulin secretion by polyclonally activated B cells (21). IL-12 has an upregulatory effect on the in vivo synthesis in mice of immunoglobulin G2a (IgG2a) (4, 6, 16, 20, 34, 38) and IgG2b (16, 20), which are associated with responses of the Th1 phenotype (7, 13, 30, 51, 52). Somewhat surprisingly, in light of its Th1-promoting effects, IL-12 treatment can also serve as a positive stimulus for the synthesis of T-helper type 2 (Th2)-associated isotype IgG1 in mice (4, 6, 16). Furthermore, IL-12 has been shown to heighten protective humoral responses that develop upon multiple exposures to irradiated cercariae, enhancing parasite-specific IgG1, IgG2a, and Saikosaponin B IgG2b responses while reducing total serum IgE responses (61). Thus, in addition to its well-established role in promoting cellular immunity, IL-12 can be envisioned as an adjuvant with potential power for the enhancement of protective humoral responses in models of antischistosome vaccination. Despite the fact that the irradiated cercarial vaccine has been quite effective in experimental settings and has proven Saikosaponin B to be an invaluable model for studying antischistosome immunity, a vaccination protocol with live parasites would be impractical for use in humans. For this reason, most efforts have focused on nonliving vaccines (examined in recommendations 3, 9, 29, 49, and 53). Our laboratory has produced an experimental vaccine (portion S3) which consists of antigens prepared by detergent extraction of worms (1). When administered intramuscularly to rats as an alum precipitate, S3 prepared from immature (4-week) parasites induces partial protective immunity (28 to 36%, depending on the dose) which is largely transferable with serum (26). S3 from adult (7-week) worms has not previously been evaluated for protective efficacy, although it is known that this.