Pre-clinical evaluation of glycosylphosphatidylinositol (GPI) as a potential universal malaria vaccine

Abstract

Malaria is a major global health burden, causing approximately 627, 000 deaths annually, especially in children under the age of five. There are five Plasmodium species that infects humans, of which Plasmodium falciparum (P.f.) and Plasmodium vivax(P.v.)are the two most prevalent. Currently, no effective vaccine against malaria exists, hence the global effort aim to develop a vaccine to prevent infection, limit disease and interrupt mosquito transmission for all Plasmodium species.Glycosylphosphatidylinositol (GPI) is a potential target as it isa conserved glycolipid anchor of many essentialparasite proteinsfound across mostdifferentiated stages and Plasmodium species. Additionally, GPI is also a toxin that causes immuno-pathological symptoms of malaria. Previously, we proved that vaccination against GPI protects mice against severe malarial disease. This study further investigates the potential of the synthetic anti-GPI vaccine in preventing infection and blocking parasite transmission into the mosquito vector in a pre-clinical rodent malaria model, P. berghei (P.b.). The vaccine showed significant efficacy in reducing liver, blood stage infection and parasite transmission to the mosquito vector independently. When mouse liver infection was left to progress through to blood stage infection and parasite uptake by the mosquitoes,remarkable reduction in oocyst numbers were observed in mosquitoes fed on vaccinated mice compared to those fed on control mice. This suggests cumulative anti-GPI antibodies generated from the vaccine have stronger parasite transmission blocking activity. This was further validated by passively immunizing mice with anti-GPI antibodies prior to mosquito infection and preliminary data showed similar reduction in oocyst burden in this group of mosquitoes.