Tegan A Don1, Jeffrey M Bethony, Alex Loukas. 1. Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research, 300 Herston Rd, Brisbane 4006, Queensland, Australia.
Abstract
BACKGROUND: Schistosomes are parasitic blood flukes that inhabit the portal blood system of humans. Ingested red cells are lysed in the gastrodermis to enable the parasites to digest hemoglobin. Saposin-like proteins (SAPLIPs) have been reported from the gastrodermis of related flukes, and at least one is hemolytic and a promising vaccine antigen. We now provide the first report of SAPLIPs from schistosomes and explore their role in host-parasite interactions. METHODS: We identified expressed sequence tags encoding a family of SAPLIPs from Schistosoma mansoni and produced one (termed Sm-SLP-1) in recombinant form using baculovirus. The anatomic site of SLP-1 expression within the worm was assessed and its recognition by sera from chronically infected humans and mice was determined. The vaccine efficacy of Sm-SLP-1 was tested in a mouse model. RESULTS: Full-length sequences were obtained for two cDNAs, Sm-slp-1 and Sm-slp-2. The Sm-slp-1 open reading frame contained a single SAPLIP domain while Sm-slp-2 had a double domain. Sm-SLP-1 was immunolocalized to the gastrodermis of adult worms, but did not confer protection in a murine vaccination model of schistosomiasis. Mice infected with S. mansoni generated a specific antibody response to Sm-SLP-1. Individuals who were infected with S. mansoni had IgG that recognized Sm-SLP-1. IgG levels were statistically higher in individuals with heavy infection. CONCLUSIONS: Sm-SLP-1 is expressed in the gastrodermis of S. mansoni. It is immunogenic in humans and mice, but is not protective as a vaccine in its current form. Schistosome SAPLIPs warrant further attention to elucidate their roles in host-parasite interactions and to further explore their potential as vaccine and diagnostic antigens.
BACKGROUND: Schistosomes are parasitic blood flukes that inhabit the portal blood system of humans. Ingested red cells are lysed in the gastrodermis to enable the parasites to digest hemoglobin. Saposin-like proteins (SAPLIPs) have been reported from the gastrodermis of related flukes, and at least one is hemolytic and a promising vaccine antigen. We now provide the first report of SAPLIPs from schistosomes and explore their role in host-parasite interactions. METHODS: We identified expressed sequence tags encoding a family of SAPLIPs from Schistosoma mansoni and produced one (termed Sm-SLP-1) in recombinant form using baculovirus. The anatomic site of SLP-1 expression within the worm was assessed and its recognition by sera from chronically infected humans and mice was determined. The vaccine efficacy of Sm-SLP-1 was tested in a mouse model. RESULTS: Full-length sequences were obtained for two cDNAs, Sm-slp-1 and Sm-slp-2. The Sm-slp-1 open reading frame contained a single SAPLIP domain while Sm-slp-2 had a double domain. Sm-SLP-1 was immunolocalized to the gastrodermis of adult worms, but did not confer protection in a murine vaccination model of schistosomiasis. Mice infected with S. mansoni generated a specific antibody response to Sm-SLP-1. Individuals who were infected with S. mansoni had IgG that recognized Sm-SLP-1. IgG levels were statistically higher in individuals with heavy infection. CONCLUSIONS: Sm-SLP-1 is expressed in the gastrodermis of S. mansoni. It is immunogenic in humans and mice, but is not protective as a vaccine in its current form. Schistosome SAPLIPs warrant further attention to elucidate their roles in host-parasite interactions and to further explore their potential as vaccine and diagnostic antigens.
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