Development of a Novel Virus-Based Vaccine Platform for a Next-Generation Malaria Vaccine

About This Grant

PROJECT SUMMARY Plasmodium parasites are responsible for a massive worldwide disease burden, causing nearly 250 million malaria cases and 600,000 deaths each year, primarily in young children. Two species of the Plasmodium parasite cause nearly all human malaria infections: P. falciparum inflicts the vast majority of malaria-associated mortality while P. vivax is more widespread and poses unique challenges to treatment. A highly effective, long- lasting, and affordable vaccine against both species of malaria is desperately needed. The two approved vaccines targeting P. falciparum are poised to significantly reduce malaria-related mortality in children. These vaccines both consist of recombinant proteins administered with an adjuvant to stimulate a robust immune response. The incomplete immunity conferred by these vaccines, along with the high healthcare burden of a multi-dose, booster-dependent vaccine compels a new approach. The goal of this proposal is to develop a heterologous vesicular stomatitis virus prime-virus like vesicle boost vaccine regimen for malaria that can generate protective cellular and humoral immunity to multiple antigens present at multiple stages of the parasite life cycle. This strategy is based on our data demonstrating that targeting additional lifecycle stages of the parasite can rescue the sub-sterilizing protection of targeting the sporozoite stage alone as is done by currently licensed vaccines. This will be paired with strategies to specifically target the responding immune cells to the liver and launch these virus-like vesicles from DNA or mRNA to increase flexibility and deliverability. Together, we believe that this one- or two-dose, multi-stage strategy will be transformative in the field of malaria vaccinology, allowing us to pursue more extensive funding to thoroughly test this strategy in the preclinical setting.