Understanding the early steps of the adaptive immune response to differentially-effective vaccines during chronic schistosomiasis

Abstract

Schistosomiasis is the second most burdensome parasitic disease in the world after malaria and is classified as a neglected tropical disease. Schistosomiasis is caused by an immunomodulatory helminth that can induce a Th2 biased response, which can cause Tc1 vaccine failure. Interestingly, the use of pathogenic Listeria monocytogenes vaccine vectors can overcome this failure through an unknown mechanism. Despite the promise of Listeria-vectored vaccines, there is reluctance among the vaccine community and the public to incorporate this vector into immunization programs, due to safety concerns. Here we ask what the question: Why do Listeria vaccines function when other methods, such as DNA vaccination, fail? To answer this question, we use bone-marrow derived dendritic cells (BMDCs) in vitro to model the development of vaccine immunity during the early steps of the adaptive immune response. To compare the immune environment in naïve and schistosome-infected vaccine recipients, we compare responses from both reactogenic DC1 and tolerogenic DC2 dendritic cells, respectively. The DC1 and DC2 subtypes are exposed to a DNA vaccine for HIV, a Listeria vaccine expressing the HIV-1 Gag protein, or left untouched. Through immunological and transcriptomic approaches, we examine these cells for their activation state and functionality; these results will help to elucidate the mechanism/s by which Listeria vectors can overcome schistosome-induced vaccine failure and identify unique molecular vaccine adjuvants functional in schistosome-endemic areas.