Schistosome vaccine testing: lessons from the baboon model

Coulson, Patricia S.; Kariuki, Thomas

doi:10.1590/s0074-02762006000900061

Cited by 6 publications

(5 citation statements)

References 17 publications

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“…However, IgM responses to immunization were recorded even though they appeared to be short-lived. Similar tendency for IgM levels was also observed with the RA vaccine in baboons [39]. Interestingly, in this study modest levels of antibody responses were observed for total IgA that was not the case in our previous studies with Sm-p80-pcDNA3 vaccine [14].…”

Section: Discussionsupporting

confidence: 87%

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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Section: Discussionsupporting

confidence: 87%

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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“…Conversely, distinct IgM responses to immunization were recorded even though they appeared to be short-lived. Similar trend for IgM levels was also observed with radiation-attenuated cercariae vaccine in baboons [44]. Weak responses were observed for total IgA; however, one animal which appeared to be an outlier showed a robust IgA response.…”

Section: Discussionsupporting

confidence: 76%

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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“…Baboons are an excellent model for schistosomiasis, as they are similar to humans in ontogeny, immune response (including human-like IgG subclasses), reproductive physiology, etc., and develop a human-like acute disease after natural or experimental exposure to S. mansoni ( 38 – 40 ). In addition, since issues of vaccine safety are also difficult to address in mice, another advantage of testing schistosome vaccines in baboons is the opportunity to address many of the deficiencies of mouse studies ( 38 – 41 ). We have also previously used baboons to successfully investigate the immune mechanisms associated with other schistosome vaccine candidates ( 42 ).…”

Section: Discussionmentioning

confidence: 99%

Protective Potential of Antioxidant Enzymes as Vaccines for Schistosomiasis in a Non-Human Primate Model

et al. 2015

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Schistosomiasis remains a major cause of morbidity in the world. The challenge today is not so much in the clinical management of individual patients, but rather in population-based control of transmission in endemic areas. Despite recent large-scale efforts, such as integrated control programs aimed at limiting schistosomiasis by improving education and sanitation, molluscicide treatment programs and chemotherapy with praziquantel, there has only been limited success. There is an urgent need for complementary approaches, such as vaccines. We demonstrated previously that anti-oxidant enzymes, such as Cu–Zn superoxide dismutase (SOD) and glutathione S peroxidase (GPX), when administered as DNA-based vaccines induced significant levels of protection in inbred mice, greater than the target 40% reduction in worm burden compared to controls set as a minimum by the WHO. These results led us to investigate if immunization of non-human primates with antioxidants would stimulate an immune response that could confer protection as a prelude study for human trials. Issues of vaccine toxicity and safety that were difficult to address in mice were also investigated. All baboons in the study were examined clinically throughout the study and no adverse reactions occurred to the immunization. When our outbred baboons were vaccinated with two different formulations of SOD (SmCT-SOD and SmEC-SOD) or one of GPX (SmGPX), they showed a reduction in worm number to varying degrees, when compared with the control group. More pronounced, vaccinated animals showed decreased bloody diarrhea, days of diarrhea, and egg excretion (transmission), as well as reduction of eggs in the liver tissue and in the large intestine (pathology) compared to controls. Specific IgG antibodies were present in sera after immunizations and 10 weeks after challenge infection compared to controls. Peripheral blood mononuclear cells, mesenteric, and inguinal node cells from vaccinated animals proliferated and produced high levels of cytokines and chemokines in response to crude and recombinant antigens compared with controls. All together, these data demonstrate the potential of antioxidants as a vaccine in a non-human primate model.

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Schistosome vaccine testing: lessons from the baboon model

Cited by 6 publications

References 17 publications

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

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

Protective Potential of Antioxidant Enzymes as Vaccines for Schistosomiasis in a Non-Human Primate Model

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