T and B Cell Reactivity to a 42‐kDa Protein Is Associated with Human Resistance to Both Schistosomiasis Mansoni and Haematobium

Abstract

Egyptian subjects living in areas endemic for Schistosoma mansoni or Schistosoma haematobium were selected on the basis of their apparent extremes of resistance or susceptibility to schistosomiasis and examined for T and B cell responses against the major electrophoretically resolved protein species from soluble adult worm extracts. A 42-kDa band was specifically recognized by a significant majority of subjects resistant to schistosomiasis. The 42-kDa species (p-42) from S. mansoni and S. haematobium were immunologically cross-reactive and induced significant protection in mice and hamsters against infection with cercariae. Amino acid sequence analysis of S. mansoni p-42 showed that it consists predominantly of glyceraldehyde 3-P dehydrogenase (G3PDH), which has been shown to be preferentially recognized by the sera of Brazilian subjects resistant to schistosomiasis mansoni. The present data extend the previous findings and imply that S. mansoni-derived G3PDH represents a target of protective T and B cell-mediated antischistosomiasis immunity in humans.

Human T- and B-Cell Responses toSchistosoma mansoniRecombinant Glyceraldehyde 3-Phosphate Dehydrogenase Correlate with Resistance to Reinfection withS. mansoniorSchistosoma haematobiumafter Chemotherapy

“…Human anti-p42 antibodies were affinity purified on a nitrocellulose strip containing 42-kDa soluble adult worm antigen (SAWA) bands as previously described (18). Antibodies to purified rSG3PDH were generated in outbred Swiss mice.…”

“…Antibodies to purified rSG3PDH were generated in outbred Swiss mice. Antibody reactivity against induced bacterial lysate or SAWA was determined by Western blotting (1,18,36).…”

“…The study population were given complete medical and parasitological examinations. Stool and urine analyses were performed as described previously (18). Donors classified as susceptible and resistant were selected among adult subjects; this is an important difference between our study and reinfection studies by other groups (7,14,24).…”

“…This protein, p42, was found to consist predominantly of schistosome glyceraldehyde 3-phosphate dehydrogenase (SG3PDH) (18). Here we report expression of SG3PDH in Escherichia coli and purification of the recombinant product (rSG3PDH) to near homogeneity by a one-step chromatographic procedure and compare the T-and B-cell immune responses to rSG3PDH in patients with a history of strong resistance or susceptibility to schistosome reinfection after treatment.…”

“…In fact, several studies have shown that susceptibility to reinfection with S. mansoni or S. haematobium varies markedly among residents of areas where infection is endemic. Certain subjects resist or maintain low levels of infection for long periods of time, while others appear to be readily reinfected shortly after clearance of the parasites (7,14,18,41). Identification of the schistosome antigens that trigger the apparent protective immune responses in some humans could be a critical step toward the development of a vaccine for schistosomiasis.…”