Malaria vaccine development: recent progress towards a sporozoite vaccine

Malaria affects the lives of hundreds of millions of people. Drug therapy is becoming less effective, a vaccine has yet to be developed, and one to two million children die annually as a result of malaria. In the last 10 years, however, there has been great progress towards a vaccine. A number of important antigens have been cloned, including the circumsporozoite (CS) protein which covers the sporozoite and which is a target for antibody and cytotoxic T lymphocytes. In laboratory models, successful vaccination has been achieved with some CS constructs. Although successful immunization with irradiated sporozoites has been achieved in the laboratory, the lack of immunity following natural exposure to sporozoites in endemic countries is puzzling. Parasite variation, host genetic factors and immunological tolerance may each contribute to this situation. Identification of other important antigens and a better understanding of host immune responses to sporozoite and liver stage antigens should be important steps towards rational vaccine design.