B- and T- cell responses to novel schistosoma mansoni skin-stage antigens among infected individuals in Entebbe – Uganda.

Abstract

Background: Schistosoma mansoni is the second major parasitic cause of morbidity and mortality after P. falciparum. Early after transformation, the skin larval stage (also known as the skin schistosomulum) is a major target of antibody-mediated immune responses. Antigens unique to these vulnerable juveniles are potential vaccine candidates. Furthermore, the immunoglobulin isotype IgG may play a greater role in this response than earlier observed. Immune responses to the skin stage antigens are not known. In the present study, total IgG levels and cytokine responses to two novel skin antigens were tested. Methodology: To quantify total IgG levels to SmKK7 and SmCD59a expressed by the skin-stage of S. mansoni among infected individuals, ELISA was performed. In addition, cytokine responses to these antigens were determined by intracellular cytokine assays using flow cytometry. Principle findings: At baseline, there were significant differences in the total IgG levels between the infected (n=25) and non-infected individuals (n=20) to all antigens analysed (SEA p=0.003, SWA p<0.0001, SmKK7 p=0.058 and SmCD59a p<0.0001) except SmKK7. However, total IgG levels to all antigens tested except SEA were not boosted six months after treatment. Similarly, the end of this follow up, cytokine responses (n=6) to the skin stage antigens in the infected group did not differ from those at baseline. Conclusion: This study demonstrated that antigens expressed by the skin stage of S. mansoni are recognised by human IgG antibodies in vitro. These findings provide an essential underlying structure to identify and test other antigens that are unique to the skin stage and that are more immunogenic to elicit IgG responses, but not IgE to develop a safe preventive vaccine. Once developed as a vaccine, these antigens can be expected to work alongside treatment as they are not affected by chemotherapy for both short term and long term protection.