Generation Of Clinically-Relevant Vaccine Vectors For Use In Schistosome-Endemic Areas

Abstract Schistosomiasis is a neglected tropical disease with 200–300 million people infected worldwide. Schistosome infections are immunomodulatory and induce a Th2 biased immune response. Chronic helminth infections, such as schistosomiasis, can cause Th1/Tc1 type vaccine failure. Schistosomiasis endemicity is geographically coincident for other diseases lacking effective vaccines (HIV, TB, and Malaria). New vaccine vectors are needed to counter the immune suppression displayed during this infection. Listeria monocytogenes has shown to function as an effective vaccine vector to induce cell-mediated immune responses. Wild-type Listeria expressing HIV-Gag was previously proven to be an effective bacterial vector, however there are safety concerns with using a pathogenic vaccine vector in humans. Therefore, it is important to develop a clinically relevant vaccine that instead uses an attenuated strain to overcome safety concerns. There are genetically attenuated strains of Listeria currently in use in human clinical trials as therapeutic cancer vaccine vectors. Here, we are cloning HIV-Gag into the attenuated strains to induce strong cell mediated immunity without risk of adverse effects from the pathogenic wild-type vector. We will confirm appropriate Gag protein expression from the novel vectors using standard methodology. Further, we will confirm the functionality of these vectors in naïve and schistosome-infected animals. Our aim is that these non-pathogenic vectors will be clinically relevant for use in schistosome-endemic areas.