Vaccine potential of a recombinant glutathione S-transferase cloned from Schistosoma haematobium in primates experimentally infected with an homologous challenge

Boulanger, Denis; Warter, A; Sellin, Bertrand; Lindner, Véronique; Pierce, Raymond J.; Chippaux, Jean-Philippe; Càpron, André

doi:10.1016/s0264-410x(98)00202-3

Cited by 51 publications

(42 citation statements)

References 28 publications

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“…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%

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%

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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“…Vaccination of semipermissive rats and permissive hamsters with recombinant Sm28-GST resulted in significant reductions of worms (7), kick-starting a 20-year program on Sm28-and Sh28-GSTs as vaccine antigens. Primate trials were conducted and showed an antifecundity effect (15), and an anti-Sm28 monoclonal antibody showed antifecundity and anti-egg embryonation effects (168). This led to the clinical testing of Sh28-GST in people and the description of its immunogenicity and induction of antibodies capable of neutralizing the enzymatic activity of the recombinant protein (26,27).…”

Section: Major Candidate Vaccines and Their Protective Efficaciesmentioning

confidence: 99%

Current Status of Vaccines for Schistosomiasis

2008

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SUMMARY Schistosomiasis, caused by trematode blood flukes of the genus Schistosoma, is recognized as the most important human helminth infection in terms of morbidity and mortality. Infection follows direct contact with freshwater harboring free-swimming larval (cercaria) forms of the parasite. Despite the existence of the highly effective antischistosome drug praziquantel (PZQ), schistosomiasis is spreading into new areas, and although it is the cornerstone of current control programs, PZQ chemotherapy does have limitations. In particular, mass treatment does not prevent reinfection. Furthermore, there is increasing concern about the development of parasite resistance to PZQ. Consequently, vaccine strategies represent an essential component for the future control of schistosomiasis as an adjunct to chemotherapy. An improved understanding of the immune response to schistosome infection, both in animal models and in humans, suggests that development of a vaccine may be possible. This review considers aspects of antischistosome protective immunity that are important in the context of vaccine development. The current status in the development of vaccines against the African (Schistosoma mansoni and S. haematobium) and Asian (S. japonicum) schistosomes is then discussed, as are new approaches that may improve the efficacy of available vaccines and aid in the identification of new targets for immune attack.

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“…Due to their critical roles in parasite-host interactions, GSTs have been targeted for pharmaceutical and vaccine purposes and have demonstrated protective effects against some parasites (11,17,34). For instance, a GST from schistosomes is currently a lead vaccine candidate for human schistosomiasis caused by Schistosoma haematobium (7) and Schistosoma mansoni (4) and is undergoing phase II and phase III clinical trials (15,41).…”

mentioning

confidence: 99%

Molecular Cloning, Biochemical Characterization, and Partial Protective Immunity of the Heme-Binding GlutathioneS-Transferases from the Human HookwormNecator americanus

et al. 2010

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Hookworm glutathione S-transferases (GSTs) are critical for parasite blood feeding and survival and represent potential targets for vaccination. Three cDNAs, each encoding a full-length GST protein from the human hookworm Necator americanus (and designated Na-GST-1, Na-GST-2, and Na-GST-3, respectively) were isolated from cDNA based on their sequence similarity to Ac-GST-1, a GST from the dog hookworm Ancylostoma caninum. The open reading frames of the three N. americanus GSTs each contain 206 amino acids with 51% to 69% sequence identity between each other and Ac-GST-1. Sequence alignment with GSTs from other organisms shows that the three Na-GSTs belong to a nematode-specific nu-class GST family. All three Na-GSTs, when expressed in Pichia pastoris, exhibited low lipid peroxidase and glutathione-conjugating enzymatic activities but high heme-binding capacities, and they may be involved in the detoxification and/or transport of heme. In two separate vaccine trials, recombinant Na-GST-1 formulated with Alhydrogel elicited 32 and 39% reductions in adult hookworm burdens (P < 0.05) following N. americanus larval challenge relative to the results for a group immunized with Alhydrogel alone. In contrast, no protection was observed in vaccine trials with Na-GST-2 or Na-GST-3. On the basis of these and other preclinical data, Na-GST-1 is under possible consideration for further vaccine development.

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Vaccine potential of a recombinant glutathione S-transferase cloned from Schistosoma haematobium in primates experimentally infected with an homologous challenge

Cited by 51 publications

References 28 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

Current Status of Vaccines for Schistosomiasis

Molecular Cloning, Biochemical Characterization, and Partial Protective Immunity of the Heme-Binding GlutathioneS-Transferases from the Human HookwormNecator americanus

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