Sm-p80 based vaccination approaches and immune correlates of protection for schistosomiasis

Infections with schistosomes represent a significant global burden of human illness. It has been estimated that schistosomes infect more than 207 million people, with 779 million additional people at risk of acquiring the infection. The parasites dwell in immune hostile portal mesenteric veins of definitive hosts by employing effective immune evasion mechanisms. We hypothesize that the development of an effective vaccine would permit integration of short term effect of chemotherapy with long term effects of a vaccine. We have targeted a schistosome antigen (Sm-p80) which plays an important role in surface membrane turnover, a phenomenon widely considered to be an immune evasion mechanism. Recently, several approaches using Sm-p80 vaccine have demonstrated promising results. For example, DNA based, recombinant Sm-p80 protein, prime boost with several adjuvant formulations have provided consistent protective efficacy that is comparable to live irradiated vaccine approach. The Sm-p80 vaccine has been encouraging in both rodent and nonhuman primate models of infection and disease. Therefore, after determining the efficacy of a DNA vaccine (Sm-p80-pcDNA3) in mice and baboons, we elucidated the role of antibodies through passive immunization of naïve animals with sera or purified IgG from the Sm-p80-pcDNA3 vaccinated mice and baboons. Then, the roles of Sm-p80 specific antibodies are subsequently confirmed as the major component of protection using antibody knockout (µMt-/-; B10.129S2 (B6)-Igh-6tm1Cgn/J) mice. Finally, the significance of antibody dependent cell mediated cytotoxicity (ADCC) using lung lavage cells or lung cells of the Sm-p80 vaccinated mice has underlined as an important component of the Sm-p80 mediated protection.