Role of host antibody in the chemotherapeutic action of praziquantel against Schistosoma mansoni: identification of target antigens.
We have demonstrated previously in a mouse model that effective chemotherapy against Schistosoma mansoni with praziquantel (PZQ) is dependent upon an intact host antibody response. In the same study, it was found that worms recovered from PZQ-treated animals display surface-bound antibodies. In order to identify the target antigens of the antibodies involved in the synergy between PZQ and the immune response, monoclonal antibodies (mAbs) and polyclonal antisera recognizing different tegumental components were tested by indirect immunofluorescence (IF) assay for their ability to bind in vitro to the surface of 6-week-old schistosomes perfused from nude (athymic) mice 1 h after PZQ treatment. Nude mice were used as hosts because worms from these animals were found to lack bound anti-schistosome antibodies. Only 5 of the 21 antibodies tested reacted with drug-treated worms. This indicated that the damage caused by PZQ to the schistosome tegument is restricted to specific tegumental components. Of the positive reactions, one group of antibodies gave IF patterns different from, whereas the other group gave IF reactions similar to those seen with worms perfused from immunologically intact mice. Antibodies against a schistosome esterase and alkaline phosphatase produced reaction patterns in the former category. In contrast, two out of three monoclonal antibodies recognizing different epitopes on a 200-kDa glycoprotein abundant in worm tubercles gave IF patterns very similar to those observed on schistosomes from drug-treated, intact mice. The biological significance of these reactions was confirmed by demonstrating that transfer of one of the positive monoclonal antibodies to 6-week-infected, B cell-depleted (mu-suppressed) mice reconstitutes the efficacy of PZQ treatment to normal levels. The above results suggest that the antibodies involved in the mechanism of action of PZQ react with a limited set of antigens. Furthermore, they implicate the 200-kDa tubercle protein as a major target of this response in naturally infected hosts.
Brindley
P J
PJ
Immunology and Cell Biology Section, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Strand
M
M
Norden
A P
AP
Sher
A
A
D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis; D000911:Antibodies, Monoclonal; D000947:Antigens, Helminth / Q000032:analysis*; D005455:Fluorescent Antibody Technique; D007116:Immunization, Passive; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011223:Praziquantel / Q000627:therapeutic use*; D011863:Radioimmunoassay; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000188:drug therapy* / Q000276:immunology
D000909:Antibodies, Helminth; D000911:Antibodies, Monoclonal; D000947:Antigens, Helminth; D011223:Praziquantel