DEVELOPMENT OF A VACCINE STRATEGY AGAINST HUMAN AND BOVINE SCHISTOSOMIASIS - BACKGROUND AND UPDATE

Schistosomiasis is a chronic and debilitating parasitic disease that a ffects over 200 million people throughout the world and causes about 5 00 000 deaths annually. Two specific characteristics of schistosome in fection are of primordial importance to the development of a vaccine: schistosomes do not multiply within the tissues of their definitive ho sts (unlike protozoan parasites) and a partial non-sterilizing immunit y can have a marked effect on the incidence of pathology and on diseas e transmission. Since viable eggs are the cause of disease pathology, a reduction in worm fecundity whether or not accompanied by a reductio n in parasite burden is a sufficient goal for vaccine induced immunity . We originally showed that IgE antibodies played in experimental mode ls a pivotal role for the development of protective immunity. These la boratory findings have been now confirmed in human populations. Follow ing the molecular cloning and expression of a protein 28 kDa protein o f Schistosoma mansoni and its identification as a glutathion S-transfe rase, immunization experiments have been undertaken in several animal species (rats, mice, baboons). Together with a significant reduction i n parasite burden, vaccination with Sm28 GST was recently shown to red uce significantly parasite fecundity and egg viability leading to a de crease in liver pathology. Whereas IgE antibodies were shown to be cor related with protection against infection, IgA antibodies have been id entified as one of the factors affecting egg laying and viability. In human populations, a close association was found between IgA antibody production to Sm28 GST and the decrease of egg output. The use of appr opriate monoclonal antibody probes has allowed the demonstration that the inhibition of parasite fecundity following immunization was relate d to the inhibition of enzymatic activity of the molecule. Epitope map ping of Sm28 GST has indicated the prominent role of the N and C termi nal domains. Immunization with the corresponding synthetic peptides wa s followed by a decrease of 70% of parasite fecundity and egg viabilit y. As a preliminary step towards phase I human trials, vaccination exp eriments have been performed in cattle, a natural model for Schistosom a bovis. Vaccination of calves with the S. bovis GST has led to a redu ction of over 80% of egg output and tissue egg count. Significant leve ls of protection were also observed in goats after immunization with t he recombinant S. bovis GST Increasing evidence of the participation o f IgA antibodies ill protective immunity has prompted us toward the de velopment of mucosal immunization. Preliminary results indicate that s ignificant levels of protection can be achieved following oral immuniz ation with live attenuated vectors or liposomes. These studies seem to represent a promising approach towards the future development of a va ccine strategy against one of the major human parasitic diseases.