Obiettivo
Schistosomiasis is the second parasitic disease in the world after malaria. 200 millions persons are affected and 800 millions are exposed. The morbidity and mortality of schistosomiasis is caused by inflammatory reaction following the implantation of viable egg in host tissues. A drug, Praziquantel, is currently used to control the disease, but reinfection occurs within months after chemotherapy and areas of drug resistance has been reported. As stated by the WHO, a vaccine is needed to for cost efficient long term control of the disease. Vaccination and drugs would probably be used in synergy. A vaccine providing partial protection would be cost effective in such a policy.
The aim of the present demonstration project, is to document the safety and potency (immunogenicity) of the schistosome GST vaccine by performing phase IIa and phase IIb clinical trials in endemic areas. The development of the production in compliance with cGMP standards with appropriate industrial partnership will be achieved.
The recombinant 28kDa glutathione S-transferase of Schistosoma haematobium (Sh28GST) is the most promising candidate of antischistosomiasis vaccine. Sh28GST alum adjuvanted vaccine formulation has successfully passed required toxicology tests in animals. It is the only antigen ready to enter clinical trials in human and it will undergo Phase I clinical trial in healthy human volunteers in Europe early 1998. The measurable objectives are: (i) scaling-up of the production process (Industrial Partner), (ii) devlopment of the quality and the in-process controls (IPC) (Industrial Partner), (iii) production of clinical batches under cGMP conditions and etablishment of the regulatory dossiers (Industrial Partner), (iv) vaccine clinical trials Phase lla in Niger and in Senegal (Partner 1). The target population will be children (6 to 15 years old). The general vaccine formulation will be Sh28GST in Alun, administered by sub-cutaneous route. This clinical Phase lla will be completed for control of safety in local unexposed children (small scale, xlO). (v) vaccine clinical trials Phase llb in Niger and in Senegal (Partner I ). The target population will be unifected children. This clinical Phase llb will be completed for control of safety and immunogenicity in infected children (small scale, xlO),
The vaccine candidate belongs to the GST family of schisostome antigens that has been extensively studied over the last 20 years with the support of WHO and CEC funding (Biotech 2 & 4, STD 1,2 & 3 and Inco-DCI and -DC3). This very well known antigen has the outstanding capability of fighting the parasite at two stages of its human cycle. First, it reduces the worm viability following infection. Worm burden reduction of 40 to 70 % has been observed in various animal models including primates and cattle. Such an effect would on its own justify the development of a 28GST vaccine. Secondly, and most advantageously, Sh28GST vaccination lead to remarkable reduction of worm fecundity and a dramatic decrease in egg viability. Animal studies showed 75 to 94 % reduction of egg viability. Sh28GST vaccination will lead to a reduction of the worm load and the disease condition due to egg infestation. Thus, the reduction of the shedding of viable eggs by the infested host would also limit the transmission of the disease. This effect, correlated with the production of neutralizing activity of GST activity, has led to the concept of a cross-species specific antifecundity vaccine. Indeed, this antifecundity immunity has been shown to be cross protective against other schistosomes because of the conservation of specific major epitopes between schistosome 28GSTs from different species (S. mansoni vs S. haematobium in primates, S. bovis vs S. mattheii in calves). Moreover, immuno-epidemiological studies in human population from areas endemic for S. mansoni or S. haematobium have clearly shown the association of the lately acquired anti-28GST immune response and the resistance to re-infection.
Sh28GST has been chosen rather than GST from other schistosomes because of its original features that make it most useful in human clinical trials. The efficacy of vaccination can be addressed by measuring the rate of re-infestation by non invasive methods such as urinary tract and bladder ultrasound tomography. The reduction of egg viability can be easily measured by numeration of eggs in filtered urine. In one of the S. haematobium endemic area selected for the trial, S mansoni is also present and the cross protection can be evaluated. Finally, the existence of a demonstrated synergy between induced-antiSh28GST immunity and Praziquantel efficacy opens a particular opportunity to evaluate the efficacy of the association with in human, in comparison with chemotherapy alone.
The present proposal does not need further laboratory research and introduces a novel control measure for schistosomiasis., which is vaccination. Accumulation of very significant data in a large number of animal models including primates, and the knowledge of the immune status of the target populations, strongly limit the risk of technological failure of this project.
No other vaccine against schistosomiasis has been proposed on the market so far. The present project introduces the first vaccine formulation able to reach the demonstration stage. This formulation would represent the most economic and durable control measure of the disease. Moreover, this new technology will not be in competition with other present methods of control (chemotherapy), since it will be used in association.
Campo scientifico (EuroSciVoc)
CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP. Cfr.: Il Vocabolario Scientifico Europeo.
CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP. Cfr.: Il Vocabolario Scientifico Europeo.
- scienze mediche e della salute scienze della salute malattie infettive malaria
- scienze mediche e della salute medicina di base immunologia
- scienze mediche e della salute medicina di base farmacologia e farmacia farmacoresistenza
- scienze mediche e della salute medicina di base farmacologia e farmacia farmaci vaccini
- scienze mediche e della salute medicina di base tossicologia
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Programma(i)
Programmi di finanziamento pluriennali che definiscono le priorità dell’UE in materia di ricerca e innovazione.
Programmi di finanziamento pluriennali che definiscono le priorità dell’UE in materia di ricerca e innovazione.
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Gli inviti a presentare proposte sono suddivisi per argomenti. Un argomento definisce un’area o un tema specifico per il quale i candidati possono presentare proposte. La descrizione di un argomento comprende il suo ambito specifico e l’impatto previsto del progetto finanziato.
Gli inviti a presentare proposte sono suddivisi per argomenti. Un argomento definisce un’area o un tema specifico per il quale i candidati possono presentare proposte. La descrizione di un argomento comprende il suo ambito specifico e l’impatto previsto del progetto finanziato.
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Procedura per invitare i candidati a presentare proposte di progetti, con l’obiettivo di ricevere finanziamenti dall’UE.
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Meccanismo di finanziamento (o «Tipo di azione») all’interno di un programma con caratteristiche comuni. Specifica: l’ambito di ciò che viene finanziato; il tasso di rimborso; i criteri di valutazione specifici per qualificarsi per il finanziamento; l’uso di forme semplificate di costi come gli importi forfettari.
Coordinatore
59019 Lille
Francia
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