Development of a vaccine strategy against human and bovine schistosomiasis: background and update

Abstract

Schistosomiasis is a chronic and debilitating parasitic disease that affects over 200 million people throughout the world and causes about 500,000 deaths annually. Two specific characteristics of schistosome infection are of primordial importance to the development of a vaccine: schistosomes do not multiply within the tissues of their definitive hosts (unlike protozoan parasites) and a partial non-sterilizing immunity can have a marked effect on the incidence of pathology and on disease transmission. Since viable eggs are the cause of disease pathology, a reduction in worm fecundity whether or not accompanied by a reduction in parasite burden is a sufficient goal for vaccine induced immunity. We originally showed that IgE antibodies played in experimental models a pivotal role for the development of protective immunity. These laboratory findings have been now confirmed in human populations. Following the molecular cloning and expression of a protein 28 kDa protein of Schistosoma mansoni and its identification as a glutathion S-transferase, immunization experiments have been undertaken in several animal species (rats, mice, baboons). Together with a significant reduction in parasite burden, vaccination with Sm28 GST was recently shown to reduce significantly parasite fecundity and egg viability leading to a decrease in liver pathology. Whereas IgE antibodies were shown to be correlated with protection against infection, IgA antibodies have been identified 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.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of glutathione-S-transferase in anti-cancer drug resistance

“…Investigations are underway to utilize the X-ray crystal structure of the malarial parasite's GST in the development of a structure-based drug design (Harwaldt et al, 2002). Schistosomiasis, a debilitating tropical disease caused by the parasite Schistosoma japonicum, affects over 200 million people worldwide and results in about 500 000 deaths annually (Capron et al, 1995;Harwaldt et al, 2002). Present therapy for the disease uses oltipraz, a drug that binds directly to the schistosome GST in the integument of the trematode (Nare et al, 1992).…”

“…One such antigen that is a potential vaccine is the 28-kDa S. mansoni GST (Sm28GST) that confers protective immunity in transgenic mice expressing Sm28GST (Nare et al, 1992;Xu et al, 1997).Vaccination with Sm28GST was shown to decrease parasite fecundity and egg viability, thereby decreasing host pathology in rats, mice, and baboons. Following vaccination in human populations, an inverse correlation was found between IgA antibody production to Sm28GST and a decrease in parasitic egg production (Capron et al, 1995). An alternative vaccine directed against the S. haematobium GST (Sh28GST) has been shown to be well tolerated in Phase I and II clinical trials, and demonstrated the ability to block transmission of the parasite (Capron et al, 2001).…”

Human Immune Responses toSchistosoma mansoniVaccine Candidate Antigens

“…Both high levels of specific immunoglobulin E (IgE) in sera and gamma interferon (IFN-␥) in antigen-stimulated peripheral blood mononuclear cell (PBMC) cultures were associated with resistance to reinfection (1,22,24,25,27,28,56,57). These data suggest the participation of immunological mechanisms in human resistance to Schistosoma mansoni infection, with mixed cellular and humoral responses.Several S. mansoni antigens have been identified and tested in experimental models, with the induction of variable levels of protection against infection (11,32,49,59,61,(68)(69)(70)74). The World Health Organization (WHO) has selected six of these antigens for further in vitro studies with PBMC from subjects in areas of endemicity for schistosomiasis.…”

“…The possibility of a schistosomiasis vaccine as an additional measure to control the disease arose from the fact that the parasite does not multiply in human beings and that reduction of infection levels by schistosomicidal drugs reduces the prevalence of severe forms of the disease. Moreover, in experimental models, partial immunity can be induced by vaccination with irradiated cercariae or specific antigens (2,11,14,26,36,37,58,59). Immunological studies of subjects from areas of endemicity have demonstrated a naturally occurring resistance to reinfection (4, 19, 22-25, 27, 28).…”

Evaluation of the immunological effect of beta alanyl-l-histidine against Schistosoma mansoni antigens in rabbits

“…To date, a vaccine based on irradiated cercariae offers almost complete protection in experimental animals [2]. The first generation vaccines were directed against infection and/or worm fecundity but currently there is a natural balance, tempering anti-schistosomal responses by stimuli down-regulating the granulomatous reaction against eggs in the tissue [3]. Fasciola spp.…”