Despite intense efforts over the past 50 years to develop a vaccine, there is currently no licensed malaria vaccine available. The limited success in inducing sufficient protection against malaria... Show moreDespite intense efforts over the past 50 years to develop a vaccine, there is currently no licensed malaria vaccine available. The limited success in inducing sufficient protection against malaria with subunit-vaccines has renewed an interest in whole-parasite vaccination strategies. While live-vaccines are hard to formulate and administer, they have been shown to confer long-lasting sterile immunity in humans. The aim of the work described in this thesis was to genetically engineer and characterize growth- and virulence-attenuated blood stage parasites (GAPBS) in the rodent malaria model, P. berghei. Specifically, the identification of GAPBS that produce only short-lived, low-level infections that can provoke strong and long-lasting protective immunity. The thesis describes improved methods to produce and screen potential GAPBS, specifically transfection methods to generate GAPBS and methods to analyze their blood stage growth-characteristics. In addition, we report the generation and characterization of a number of novel GAPBS that are virulence-attenuated and produce self-resolving infections in mice. These GAPBS are useful tools to better understand the induction of protective immunity against Plasmodium blood stages and may help to create an effective and broad acting antimalarial vaccine. Show less
