Such a delay in the expression of protective effects has been observed in patas monkeys experimentally infected with after vaccination with 28GST (6)

Such a delay in the expression of protective effects has been observed in patas monkeys experimentally infected with after vaccination with 28GST (6). in humans, IgG antibodies in calves with schistosomiasis may exhibit inhibitory functions toward GST enzymatic activity or have a modulatory effect on IgA antibody properties. Furthermore, sera from animals immunized with recombinant 28GST acknowledged the native 28GST and achieved comparable Rabbit Polyclonal to SHIP1 levels of inhibition of activity of Pipequaline recombinant 28GST and 28GST, indicating the presence of cross-reactive epitopes on these two molecules. During the past few years, the increasing interest devoted to the development of the immunological control of schistosome infections has led, through the introduction of monoclonal antibody and molecular biology methodologies, to the characterization of a number of schistosome antigens exhibiting protective properties towards schistosome challenge infections. Among these many vaccine candidates, schistosome 28-kDa glutathione (1, 2), the protein has been cloned, sequenced, and expressed in both and (2). The native and recombinant proteins were shown to induce highly significant levels of protection in various animal models, such as mice, rats, hamsters, and baboons (2, 3, 4, 10). This protection led to a reduction of worm burden (3) and/or an impairment of parasite fecundity, the latter having potentially major consequences for the development of egg-related pathology, e.g., granuloma formation (4). Protective effects of GST were also demonstrated against experimental infections in ruminants (5, 7). Immunization of calves with native GSTs induced a reduction of the egg burden without any effect on the number of worms (7), whereas vaccination of goats with the recombinant Pipequaline 28GST) affected worm counts with no impairment of Pipequaline fecundity (5). The mechanisms underlying the protection induced by immunization with the 28GST have been studied with monoclonal antibodies. The effect upon fecundity seems to be linked to the inactivation of the enzymatic activity, whereas the reduction of the worm burden appears to be independent of the GST enzyme activity (32). In human schistosomiasis, specific immunoglobulin A (IgA) antibodies to 28GST, which displayed a neutralizing effect on the enzymatic activity of the molecule, have been shown to significantly impair in vitro the egg laying of female worms and the hatching of eggs (12). The existence of a link between the inactivation of the enzymatic activity of 28GST and the effect on fecundity is further supported by the data collected from immunization experiments involving synthetic peptides derived from the primary structure of 28GST. Immunization with the N- or C-terminal peptides involved in the catalytic site of the molecule mainly affects worm fertility, whereas immunization with the central peptide from positions 115 to 131 induces a reduction of the worm burden (22, 31, 33). Comparative analysis of the 28GST sequences undertaken with different species of schistosomes revealed slight amino acid variations in the central peptide from positions 115 to 131, supporting the species specificity and a highly conserved structure for the C- and N-terminal peptides (29). The latter could explain the significant decrease of egg production recorded for primates (28GST (6). Recently, we were able to demonstrate that immunization of calves with recombinant 28GST induced significant reductions in the female worm burdens, fecal egg counts, and excretion of viable eggs, as determined by miracidial counts, in animals exposed to natural infection in the field (8). In contrast, the same immunization had no protective effect against a heavy experimental challenge with 28GST to protect cattle against infection (8). These studies involved a total of 28 castrated male calves (Friesian) aged 4 to 6 6 months. The calves were divided by live weight into two equal groups of 14 calves each. The first group received two intramuscular injections of 0.250 mg of recombinant 28GST in phosphate-buffered saline (PBS) emulsified in an equal volume of complete Freunds adjuvant (CFA; Sigma) at a 3-week interval (vaccinated group). The second group also received two injections but with PBS emulsified in CFA only (control group). All calves were then challenged 2 weeks after the second inoculation (vaccinated calves; = 14) or adjuvants alone (controls; = 14). In the first experiment, seven vaccinated and.