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No vaccines are available for human use for any parasitic infections, including the helminthic disease schistosomiasis. Sm-p80, the large subunit of Schistosoma mansoni calpain, is a leading antigen candidate for a schistosomiasis vaccine. Prophylactic and antifecundity efficacies of Sm-p80 have been tested using a variety of vaccine approaches in both rodent and nonhuman primate models. However, the therapeutic efficacy of a Sm-p80-based vaccine had not been determined. In this study, we evaluated the therapeutic efficacy of Sm-p80 by using 2 different strategies and 3 Sm-p80-based vaccine formulations in baboons. Vaccine formulations were able to decrease established adult worms by 10%-36%, reduce retention of eggs in tissues by 10%-57%, and decrease egg excretion in feces by 13%-33%, compared with control formulations. Marked differences were observed in B and T cell immune correlates between vaccinated and control animals. This is the first report of killing of established adult schistosome worms by a vaccine. In addition to distinct prophylactic efficacy of Sm-p80, this study adds to the evidence that Sm-p80 is a potentially important antigen with both substantial prophylactic and therapeutic efficacies. These data reinforce that Sm-p80 should be moved forward along the path toward human clinical trials. [ABSTRACT FROM AUTHOR]

The prophylactic efficacy of a schistosome antigen (Sm-p80)was tested in a nonhuman primatemodel, the baboon. Using a total of 28 baboons, different vaccination strategies were used including recombinant Sm-p80 protein formulated in Toll-like receptor 7 and Toll-like receptor 9 agonists, and DNA priming followed by boosting with protein plus adjuvants. Recombinant protein approaches provided levels of prophylactic efficacy of 52%-58%, whereas prime-boost approaches conferred 38%-47% protection in baboons. An appropriately balanced proinflammatory (T-helper 17 [Th17] and Th1) and anti-inflammatory (Th2) type of response was generated; the Th1 and Th17 types of immune responses appear to be indicative of increased prophylactic efficacy. Production and expression of several cytokines (interleukin 2 [IL-2], interferon &ggr;, IL-12&agr;, IL-1&bgr;, IL-6, and IL-22)were up-regulated in vaccinated animals. Human correlate studies revealed Sm-p80 reactivity with immunoglobulin G in human serum samples from schistosome-infected individuals. In addition, a complete lack of prevailing Sm-p80-specific immunoglobulin E in a high-risk or infected populationwas observed, thusminimizing the risk of hypersensitivity reaction following vaccination with Sm-p80 in humans. This study provided the proof of concept tomove Sm-p80 forward into further preclinical development leading to human clinical trials. [ABSTRACT FROM AUTHOR]

To date, no vaccine is available to prevent human schistosomiasis. We have targeted a protein of Schistosoma mansoni that plays an important role in the surface membrane renewal process, a mechanism widely believed to be utilized by the parasite as an immune evasion strategy. Sm-p80 antigen is a promising vaccine target because of its documented immunogenicity, protective efficacy, and antifecundity effects observed in both experimental murine and nonhuman primate models of this infectious disease. In the present study, we report that, in a vector approved for human use (VR1020), an Sm-p80-based DNA vaccine formulation confers a 46% reduction in the worm burden in a baboon (Papio anubis) model. Baboons vaccinated with Sm-p80- VR1020 had a 28% decrease in egg production after challenge with the infectious parasite. Sm-p80-VR1020 vaccine elicited robust immune responses to specific antigen Sm-p80, including immunoglobulin (Ig) G, its subtypes IgG1 and IgG2, and IgA and IgM in vaccinated animals. When stimulated in vitro with recombinant Sm-p80, peripheral blood mononuclear cells and splenocytes from baboons vaccinated with Sm-p80-VR1020 produced considerably higher levels of T helper 1 response-enhancing cytokines (interleukin [IL]-2 and interferon-γ) than T helper 2 (Th2) response-enhancing cytokines (IL-4 and IL-10). Peripheral blood mononuclear cells produced a significantly higher number of spot-forming units for interferon-γ than for IL-4 in enzyme-linked immunosorbent spot assays. A mixed T helper 1/T helper 2 type of humoral and T cell responses was generated after immunization with Sm-p80-VR1020. These findings again highlight the potential of Smp80 as a promising vaccine candidate for schistosomiasis. [ABSTRACT FROM AUTHOR]