Immunization of mice and baboons with the recombinant Sm28GST affects both worm viability and fecundity after experimental infection with Schistosoma mansoni

Abstract

A member of the glutathione S-transferase family, Sm28GST has previously demonstrated a good ability to protect rodents against experimental infection with Schistosoma mansoni. In order to evaluate its efficacy in a model closer to man, two different protocols of immunization with recombinant Sm28GST were tested on baboons in a large-scale trial. Three injections in the presence of aluminium hydroxide as adjuvant resulted in a significant 38% reduction in the adult worm burden together with a trend for a lower percentage of inflammatory tissue in the liver. Individual levels of protection, ranging from 0 to 80%, underlined the heterogeneity of the immune response to this purified molecule in outbred primates. On the other hand, two injections of Sm28GST in the presence of aluminium hydroxide and Bordetella pertussis reduced female schistosome fecundity by 33%, with a more pronounced effect (66%) on faecal egg output; there was also a trend, in this protocol, for decrease of the mean granuloma surface in the liver. Individual anti-Sm28GST IgG antibodies were apparently unrelated to levels of immunity, but there was partial evidence that cytophilic IgE might play a role in the immune mechanisms affecting worm viability, but not fecundity. In the mouse model, Sm28GST vaccination resulted in a lower hatching ability of tissue eggs recovered from immunized mice whereas passive transfer of specific anti-Sm28GST T-lymphocytes, one day before infection, significantly reduced the number of eggs in the liver of mice. We propose that different protocols of immunization with a recombinant molecule can impede Schistosoma mansoni worm viability and fecundity, but can also affect miracidium physiology, with important consequences for disease transmission and granuloma-derived pathology.

The serological differentiation of acute and chronic schistosomiasis japonica using IgA antibody to egg antigen

“…Recently it has been demonstrated that IgA antibody to a 28-KD glutathione-s-transferase of S. mansoni seemed to play a protective role in patients with schistosomiasis, limiting egg laying and hatching (Grzych et al 1993) and reducing the pathology related to the formation of egg granulomas (Boulanger et al 1991).…”

Deletion Analysis of the Schistosoma Mansoni 28‐kDa Glutathione S‐transferase Gene Promoter in Mammalian Cells

“…Sm28GST also represents a major antigen of S. munsoizi. Immunization with recombinant Sm28GST generated partial protection to infection in rodents and monkeys (Balloul et al, 1987;Boulanger et al, 1991). Even though the mechanisms by which anti-Sm28GST antibodies protect against infection still remain to be defined, the presence of antibodies blocking the Sm28GST activity was positively correlated with the reduction of female fecundity and egg viability in vitro and in vivo (Xu et al, 1991(Xu et al, , 1993.…”

“…This enzyme displays limited structural similarity and enzymatic activities characteristic of a, p, and TC class GST enzymes (Walker et al, 1993). Sm28GST was also shown to be a major parasite antigen; immunisation with the purified or recombinant enzyme induced protection against infection in different experimental models (Balloul et al, 1987a;Boulanger et al, 1991). Very little is known about the regulation of the expression of this enzyme.…”

Parasite Vaccines: Recent Progress in, and Problems Associated with their Development

“…Sm28-GST is expressed in the sub-tegumental tissues of the parasite and vaccination studies in rats and hamsters with the S. haematobium equivalent [55] indicated its significant protective potential. Trials in primates demonstrated an anti-fecundity effect [56]. Clinical testing of Sh28-GST in people showed that the vaccine was immunogenic and antibody inhibited the enzymatic activity of the recombinant protein [57].…”