ACTIVITY 6 - HUMORAL/CELLULAR RESPONSE IN MICE - FHEPATICA VACCINE CANDIDATE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A novel F. hepatica Ag was recently cloned and characterized. It is a member of the F. hepatica saposin-like protein family which is expressed by parasite at early stages of infection and when it is injected in rabbits induce a strong resistance to a challenge infection. Previous immunization studies in mice have revealed that FhSAP-2 induce a mixed Th1/Th2 response, which is slightly polarized to Th1 when is delivered as DNA vaccine. It has been demonstrated that in chronic fascioliasis the infection is associated to Th2 response. However, in animals than develop a natural resistance to infection high levels of IgG2 and IFNg characteristic of a Th1 type response have been observed. Thus, the Th1 response appears to be necessary for inducing resistance to infection. A previous result obtained from our group suggests that FhSAP-2 is a Fasciola/Schistosoma cross-reactive antigen. Because of the heterologous immunity between both species has been demonstrated it is possible that FhSAP-2 could form part of a multi-component vaccine against both diseases. Thus, FhSAP-2 has become in a novel promising vaccine candidate that could also constitute the base for a dual-Fasciola/Schistosoma vaccine. Additional preliminary results need to be compiled before to initiate large vaccination trials. We previously demonstrated that FhSAP-2 induces significant protection against a challenged infection. However, in that study we failed to determine whether this protection is Th1-biased or Th2-biased. In the mouse study we evaluated the immune response after immunization with FhSAP-2 and showed that Th1-biased response may be predominant, but failed to determine whether this immunization protocol conferred any protection. We also demonstrated that FhSAP-2 is a Fasciola/Schistosoma cross-reactive Ag. However, the simple cross-reactivity should not be the only criterion for developing a vaccine against schistosomiasis. The current proposal intends to accomplish two specific aims. In the Aim1 we will characterize the immune responses to FhSAP-2 produced in mice and we will determine if this protection is Th1-biased or Th2-biased. In the Aim-2 we will determine whether sera from mouse immunized with irradiated cercariae (the gold standard vaccine for schistosomiasis) recognize FhSAP-2 and whether a homolog FhSAP-2 exits in S. mansoni. The results to be obtained in the present pilot project will serve to submit an RO1 project in short period of time.