Developmental Clinical Studies - Clinical evaluation of an AdCh63-MVA PvDBP_RII vaccine for blood-stage Plasmodium vivax

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Malaria is one of the greatest causes of infectious mortality globally but no vaccine is available. The blood-stage of the parasite?s life-cycle is the one that causes all the symptoms of disease and very often death. Five different types of parasite cause malaria disease in humans. Most research in the last few decades has focussed on one of these parasites ? called Plasmodium falciparum. This parasite is responsible for most of the deaths every year due to malaria infection.Many vaccines against blood-stage infection with Plasmodium falciparum have been tested in clinical trials but always with disappointing results. This is most likely because this parasite has many different ways to infect red blood cells. Consequently if a vaccine stops one invasion pathway, the parasite will simply switch to a different one and continue with the infection process.A second malaria parasite, called Plasmodium vivax, is far more widespread worldwide. Although it doesn?t kill infected individuals, infection with this parasite causes a debilitating and severe illness that often relapses months or years later. This parasite, like Plasmodium falciparum, exerts a huge and unacceptable health burden on the wider developing world. However, this parasite may be more amenable to the effects of a blood-stage vaccine. It can only use a single invasion pathway to infect red blood cells, and a vaccine targeting this one pathway may stand a much greater chance of success. Here we propose to use a new vaccine delivery technology to target this invasion pathway of Plasmodium vivax. Vectored vaccines use a crippled but safe virus to produce the malaria protein inside the injection site of the vaccinee. This technology has recently been shown to be safe and capable of inducing strong immune responses in human clinical trials at Oxford University. In this application we therefore propose to test a new pair of vectored vaccines against the blood-stage of Plasmodium vivax malaria for the first time in humans. We will develop these new vaccines and test their safety and immune-stimulating capacity in a clinical trial in healthy adult volunteers. This study should provide a critical test of the possibility that such vectored vaccines could be useful in inducing immune responses that may protect people against infection with the Plasmodium vivax form of malaria.