Resistance to re‐infection after exposure to normal and attenuated schistosome parasites in the baboon model

Kariuki, Thomas; Farah, Idle O.

doi:10.1111/j.1365-3024.2005.00783.x

Cited by 19 publications

(11 citation statements)

References 73 publications

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“…Instead, decreasing the level of IL-17 in mice by injecting anti-IL-17A neutralizing mAb led to reductions of worm and egg burdens, suggesting that the decrease of IL-17 levels contributed to effective protective responses against S. japonicum infection. Our study further showed that administration of the anti-IL-17A neutralizing mAb increased the levels schistosome specific IgG1, IgG2a and/or IgG, suggesting that increased antibody-dependent-cell-cytoxicity (ADCC), one of the well accepted mechanisms of killing extra-cellular residing pathogens including schistosome [60], may at least partially contributed to the more effective protective responses against S. japonicum infection. However, the mechanism underlying the role of IL-17 in the protection against S. japonicum infection needs to be further investigated.…”

Section: Discussionsupporting

confidence: 55%

Dynamics of Th17 Cells and Their Role in Schistosoma japonicum Infection in C57BL/6 Mice

Wen

Cheng

et al. 2011

PLoS Negl Trop Dis

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BackgroundThe current knowledge of immunological responses to schistosomiasis, a major tropical helminthic disease, is insufficient, and a better understanding of these responses would support vaccine development or therapies to control granuloma-associated immunopathology. CD4+ T cells play critical roles in both host immune responses against parasitic infection and immunopathology in schistosomiasis. The induction of T helper (Th)1, Th2 and T regulatory (Treg) cells and their roles in schistosome infections are well-illustrated. However, little in vivo data are available on the dynamics of Th17 cells, another important CD4+ T cell subset, after Schistosoma japonicum infection or whether these cells and their defining IL-17 cytokine mediate host protective responses early in infection.MethodologyLevels of Th17 and the other three CD4+ T cell subpopulations and the cytokines related to induction or repression of Th17 cell generation in different stages of S. japonicum infection were observed. Contrary to reported in vitro studies, our results showed that the Th17 cells were induced along with the Th1, Th2, Treg cells and the IFN-γ and IL-4 cytokines in S. japonicum infected mice. The results also suggested that S. japonicum egg antigens but not adult worm antigens preferentially induced Th17 cell generation. Furthermore, decreasing IL-17 with a neutralizing anti-IL-17 monoclonal antibody (mAb) increased schistosome-specific antibody levels and partial protection against S. japonicum infection in mice.ConclusionsOur study is the first to report the dynamics of Th17 cells during S. japonicum infection and indicate that Th17 cell differentiation results from the integrated impact of inducing and suppressive factors promoted by the parasite. Importantly, our findings suggest that lower IL-17 levels may result in favorable host protective responses. This study significantly contributes to the understanding of immunity to schistosomiasis and may aid in developing interventions to protect hosts from infection or restrain immunopathology.

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Section: Discussionsupporting

confidence: 55%

Dynamics of Th17 Cells and Their Role in Schistosoma japonicum Infection in C57BL/6 Mice

Wen

Cheng

et al. 2011

PLoS Negl Trop Dis

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“…Similarly, immunization of baboons with IrV5 elicited a protection by 28% and visible reduction in the sizes of granulomas [35]. In baboons, radiation-attenuated (RA) cercariae vaccine has been found to be effective to varying degrees, however, multiple exposures are required to elicit high levels of protection [32, 36, 37]. For example, in one study, 50% protection was achieved after three vaccinations with RA vaccine [20] and in another study, 80% protection was achieved after four vaccinations with shorter intervals between the final boost and experimental challenge [35].…”

Section: Discussionmentioning

confidence: 99%

Sm‐p80–Based DNA Vaccine Provides Baboons with Levels of Protection againstSchistosomamansoniInfection Comparable to Those Achieved by the Irradiated Cercarial Vaccine

et al. 2010

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No vaccine is available to prevent human schistosomiasis to date. 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 this study we report that a Sm-p80-based DNA vaccine formulation, in a human use approved vector (VR1020), confers 46% reduction in worm burden in the baboon (Papio anubis) model. Baboons vaccinated with Sm-p80-VR1020 showed 28% decrease in egg production following challenge with the infectious parasite. Sm-p80-VR1020 vaccine elicited robust antigen specific immune responses that included IgG; its subtypes IgG1 and IgG2; IgA and IgM in vaccinated animals. Peripheral blood mononuclear cells (PMBCs) and splenocytes from baboons vaccinated with Sm-p80-VR1020 when stimulated in vitro with recombinant Sm-p80 produced considerably higher levels of Th1 response enhancing cytokines (IL-2, IFN-γ) than Th2 response enhancing cytokines (IL-4, IL-10). PBMCs produced significantly higher number of spot forming units (SFU) for INF-γ than for IL-4 in enzyme-linked immunosorbent spot (ELISPOT) assays. A mixed Th1/Th2 type of humoral and T cell responses were generated following immunization with Sm-p80-VR1020. These findings again highlight the potential of Sm-p80 as a promising vaccine candidate for schistosomiasis.

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“…Similarly, inoculation of baboons with IrV5 elicited a protection by 28% and noticeable reduction in the sizes of granulomas [40]. In baboons, radiation-attenuated cercariae vaccine is effective but multiple exposures are required to elicit levels of protection from 50% [41] to 80% [40;42]. However, compared to the studies that utilized defined vaccines, a Sm-p80-based DNA vaccine appears to be comparable or superior in its anti-worm and anti-fecundity effect.…”

Section: Discussionmentioning

confidence: 99%

Protective and antifecundity effects of Sm-p80-based DNA vaccine formulation against Schistosoma mansoni in a nonhuman primate model

Ahmad

Zhang

Torben

et al. 2009

Vaccine

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Schistosomiasis is an important parasitic disease for which there is no available vaccine. We have focused on a functionally important antigen of Schistosoma mansoni, Sm-p80, as a vaccine candidate because of its consistent immunogenicity, protective potential and antifecundity effect observed in murine models; and for its pivotal role in the immune evasion process. In the present study we report that a Sm-p80-based DNA vaccine formulation confers 38% reduction in worm burden in a nonhuman primate model, the baboon (Papio anubis). Animals immunized with Sm-p80-pcDNA3 exhibited a decrease in egg production by 32%. Sm-p80 DNA elicited specific immune responses that include IgG; its subtypes IgG1 and IgG2; and IgM in vaccinated animals. Peripheral blood mononuclear cells (PMBCs) from immunized animals when stimulated in vitro with Sm-p80 produced appreciably more Th1 response enhancing cytokines (IL-2, IFN-γ) than Th2 response enhancing cytokines (IL-4, IL-10). PBMCs produced appreciably more spot forming units for INF-γ than for IL-4 in enzyme-linked immunosorbent spot (ELISPOT) assays. Overall it appears that even though a mixed (Th1/Th2) type of humoral antibody response was generated following immunization with Sm-p80; the dominant protective immune response is Th1 type. These data reinforce the potential of Sm-p80 as an excellent vaccine candidate for schistosomiasis.

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Resistance to re‐infection after exposure to normal and attenuated schistosome parasites in the baboon model

Cited by 19 publications

References 73 publications

Dynamics of Th17 Cells and Their Role in Schistosoma japonicum Infection in C57BL/6 Mice

Dynamics of Th17 Cells and Their Role in Schistosoma japonicum Infection in C57BL/6 Mice

Sm‐p80–Based DNA Vaccine Provides Baboons with Levels of Protection againstSchistosomamansoniInfection Comparable to Those Achieved by the Irradiated Cercarial Vaccine

Protective and antifecundity effects of Sm-p80-based DNA vaccine formulation against Schistosoma mansoni in a nonhuman primate model

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