Conference 2021 Live Talk
An Adenovirus-Vectored Vaccine Protects from Intestinal Schistosomiasis in a Pre-Clinical Model
Authors and Affiliations
Dilhan J Perera1,2, Adam S Hassan2,3, Christine Gadoury4, Mehdi Elahi4, Renald Gilbert4, Risini Weeratna5, Momar Ndao1,2,3
1. Division of Experimental Medicine, McGill University, Montreal, Canada
2. Program in Infectious Diseases and Immunity in Global Health, Research Institute at the McGill University Health Centre, Montreal, Canada
3. Department of Microbiology and Immunology, McGill University, Montreal, Canada
4. Human Health Therapeutics Research Centre, National Research Council of Canada, Montreal, Canada
5. Human Health Therapeutics Research Centre, National Research Council of Canada, Ottawa, Canada
Schistosomiasis (Schisto) is one of the most prevalent parasitic diseases worldwide. Although >700 million people are at risk of infection, this parasite goes underestimated, and causes debilitating illnesses which can last over 30 years, such as diarrhea, blood in the stool, and in some cases bladder cancer. This project tested the protective ability of Schistosoma mansoni cathepsin B when delivered by a genetically engineered Adenovirus as a vector. Adenovirus vectored vaccines can be seen in clinical trials for Hepatitis B, malaria, HIV, among others, and are known for their potent Th1 immune responses.
Protection from infection through this vaccine was tested in our established mouse model. Elicited antibody responses after immunization was assessed by ELISA assays, and splenocytes post immunization were stimulated ex vivo with antigen and were evaluated for cytokine expression using flow cytometry, and multiplex ELISA. Adult worm burden, and egg deposition in the liver and intestines were determined after challenge with parasite.
Upon immunization with our recombinant Adenovirus, we saw robust humoral responses in avid antigen specific IgG inducing both IgG1 and IgG2c. Flow cytometry analysis of splenocytes saw increased expression of IFNy, IL2, and TNFa from CD4+ and CD8+ T cells. A multiplex ELISA was also run on splenocyte supernatants and we saw increased expression of Th1 cytokines when compared to the PBS control. Immunized mice were challenged, and our vaccine delivered parasite burden reductions of 83.1%, 84.4%, and 91.8% in adult worm burden, hepatic, and intestinal egg burdens respectively, when compared to the PBS control.
Our recombinant Adenovirus vaccine delivers schistosomiasis protection far superior to the WHO standard of 40% parasite burden reduction. Not only would an effective vaccine for schisto benefit populations in endemic regions aiding interruption of disease transmission but it would also benefit travelers to tropical regions and reduce the chance of potential outbreaks in other areas due to human migration.