Production and testing of Schistosoma japonicum candidate vaccine antigens in the natural ovine host

Mg, Taylor; Mc, Huggins; F, Shi; J, Lin; Tian, E; P, Ye; Shen, Wei; Cg, Qian; Bf, Lin; Qd, Bickle

doi:10.1016/s0264-410x(98)00055-3

Cited by 59 publications

(31 citation statements)

References 27 publications

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“…Previously identified S. haematobium antigens that were only serologically recognized post-treatment include tropomyosin, paramyosin, triose phosphate isomerase, and glutathione S-transferase (GST) (27). Vaccinations of mice and natural mammalian hosts with S. japonicum tropomyosin and paramyosin lead to modest reductions in worm burden upon challenge, and often to an even greater reduction in egg output (28,29), although this is not always seen (30,31). One study has suggested that S. japonicum triose phosphate isomerase induces anti-fecundity effects (32), but other studies show a similar reduction in worm burden as in egg output (33), suggesting other immune targets.…”

Section: Discussionmentioning

confidence: 99%

“…One study has suggested that S. japonicum triose phosphate isomerase induces anti-fecundity effects (32), but other studies show a similar reduction in worm burden as in egg output (33), suggesting other immune targets. The antigen that has been most frequently associated with an anti-fecundity response is GST, which has been shown to reduce S. haematobium worm fecundity in baboons (34) as well as S. mansoni fecundity in mice (35) and S. japonicum fecundity in natural hosts (30).…”

Section: Discussionmentioning

confidence: 99%

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Protective immunity to Schistosoma haematobium infection is primarily an anti-fecundity response stimulated by the death of adult worms

Mitchell

Mutapi

Savill

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Protective immunity against human schistosome infection develops slowly, for reasons that are not yet fully understood. For many decades, researchers have attempted to infer properties of the immune response from epidemiological studies, with mathematical models frequently being used to bridge the gap between immunological theory and population-level data on schistosome infection and immune responses. Here, building upon earlier model findings, stochastic individual-based models were used to identify model structures consistent with observed field patterns of Schistosoma haematobium infection and antibody responses, including their distributions in cross-sectional surveys, and the observed treatment-induced antibody switch. We found that the observed patterns of infection and antibody were most consistent with models in which a long-lived protective antibody response is stimulated by the death of adult S. haematobium worms and reduces worm fecundity. These findings are discussed with regard to current understanding of human immune responses to schistosome infection. acquired immunity | immunoepidemiology | schistosomiasis

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Protective immunity to Schistosoma haematobium infection is primarily an anti-fecundity response stimulated by the death of adult worms

Mitchell

Mutapi

Savill

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…It acts as one of the major schistosome immunogens during infection with S. mansoni in mice (27) and humans (47). Vaccination trials performed with S. mansoni (16,42) or S. japonicum (6,35,53) infections in mice, pigs, or water buffaloes demonstrated that immunization with native or recombinant paramyosin can reduce the worm burden and liver or fecal egg counts in infected animals. It will soon become clear whether or not paramyosin exerts a similar vaccination activity in humans (2).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the Complement Membrane Attack Complex bySchistosoma mansoniParamyosin

Deng¹,

Gold²,

LoVerde

et al. 2003

Infect Immun

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Following partial purification and analysis by mass spectrometry, we have determined SCIP-1 to be a surface-exposed form of the muscle protein paramyosin. As shown by immunofluorescence, anti-paramyosin antibodies label the surface of live schistosomula and adult worms. Like SCIP-1, purified native paramyosin reacts with a polyclonal rabbit anti-human CD59 antiserum, as shown by Western blot analysis. Also, the human complement components C8 and C9 bind to recombinant and native paramyosin. Analysis of paramyosin binding to fragments of C9 generated by thrombin or trypsin has demonstrated that paramyosin binds to C9 at a position located between Gly245 and Arg391. Paramyosin inhibited Zn 2؉ -induced C9 polymerization and poly-C9 deposition onto rabbit erythrocytes (E R ). In addition, paramyosin inhibited lysis of E R and of sensitized sheep erythrocytes by human complement. Finally, anti-paramyosin antibodies enhanced in vitro killing of schistosomula by normal and C4-depleted human complement. Taken together, these findings suggest that an exogenous form of S. mansoni paramyosin inhibits activation of the terminal pathway of complement and thus has an important immunomodulatory role in schistosomiasis.Schistosomiasis is one of the most prevalent parasitic diseases, affecting over 200 million people who live in areas of endemicity in Africa, South America, and Asia (12). Schistosoma mansoni, one of the causative agents of this disease, resides within patients' mesenteric and portal blood systems and successfully evades host immune responses (43). During skin penetration into the mammalian host and shortly afterwards, the larvae convert from exhibiting sensitivity to complement-mediated killing to bearing resistance to complementmediated killing (32, 49). The first step in that conversion is the removal of the glycocalyx coat that contains strong complement activators. Subsequently, the transformed schistosomula and the adult worms employ several strategies to evade the host's complement system (14), thus enabling the parasite to reside for years within the host's circulatory system in direct contact with complement proteins. This parasite contains proteins that bind in vitro to the complement proteins C1 (25) and C2 (22) and C8 and C9 (40) and may thus block the complement cascade at multiple steps. Paramyosin, one of the inhibitory proteins, was shown to bind in vitro to C1q and inhibit C1 and the classical pathway of complement activation (25). Paramyosin is in essence an invertebrate muscle protein (11) that serves as a major component of the thick filament and is thought to play an important role in certain specialized contractile states (7, 23). It has also been found to be an immunogen during infection of mice and humans with helminth parasites (27,37,47). A nonfilamentous membrane-bound form of paramyosin was also found in the tegumental outer layer (16, 33) and on the surface (18, 31) of S. mansoni schistosomes. Analyzed on the basis of its capacity to bind to Fc (31), it has been suggested to have immu...

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“…However, the degree of immunity induced by leucine aminopeptidase was significantly decreased when it was combined with two cathepsin L proteinases, which on their own were moderately protective (28). In studies on Schistosoma vaccines, many candidate antigens have been identified, but in the limited data set on combinations of antigens there is little compelling data for enhanced efficacy (37).…”

Section: Discussionmentioning

confidence: 99%

Immunization with a Combination of Merozoite Surface Proteins 4/5 and 1 Enhances Protection against Lethal Challenge withPlasmodium yoelii

et al. 2002

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It is widely believed that subunit vaccines composed of multiple components will offer greater protection against challenge by malaria, and yet there is little experimental evidence to support this view. We set out to test this proposition in the Plasmodium yoelii challenge system in rodents by comparing the degree of protection conferred by immunization with a mixture of merozoite surface proteins to that conferred by single proteins. We therefore examined a defined protein mixture made of the epidermal growth factor-like domains of P. yoelli merozoite surface protein 1 (MSP1) and MSP4/5, the homologue of P. falciparum MSP4 and MSP5. In the present study we demonstrate that this combination of recombinant proteins dramatically enhances protection against lethal malaria challenge compared to either protein administered alone. Many mice immunized with the MSP4/5 plus MSP1 19 combination did not develop detectable parasitemia after challenge. Combined immunization with MSP1 19 and yMSP4/5, a product characterized by lower protective efficacy, also greatly enhanced protection by reducing peak parasitemias and increasing the numbers of survivors. In some combination trials, levels of antibodies to MSP1 19 were elevated compared to the MSP1 19 alone group; however, improved protection occurred regardless of whether boosting of the anti-MSP1 19 response was observed. Boosting of anti-MSP1 19 did not appear to be due to contaminating endotoxin in the EcMSP4/5 material since enhanced protection was observed in C3H/HeJ mice, which are endotoxin insensitive. Collectively, these experiments show that multiantigen combinations offer enhanced levels of protection against asexual stage infection and suggest that combinations of MSP1, MSP4, and MSP5 should be evaluated further for use in humans.

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Production and testing of Schistosoma japonicum candidate vaccine antigens in the natural ovine host

Cited by 59 publications

References 27 publications

Protective immunity to Schistosoma haematobium infection is primarily an anti-fecundity response stimulated by the death of adult worms

Protective immunity to Schistosoma haematobium infection is primarily an anti-fecundity response stimulated by the death of adult worms

Inhibition of the Complement Membrane Attack Complex bySchistosoma mansoniParamyosin

Immunization with a Combination of Merozoite Surface Proteins 4/5 and 1 Enhances Protection against Lethal Challenge withPlasmodium yoelii

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