Abstract
Malaria kills >1 million children each year, and there is little doubt that an effective vaccine would play a central role in preventing these deaths. However, the strategies that proved so successful in developing the vaccines we have today may simply not be adequate to confront complex, persistent infectious diseases, including malaria, AIDS, and tuberculosis. We believe that the development of a highly effective vaccine will require a better understanding of several features of the immune response to malaria. At the top of the list is the complex and ancient relationship between the parasite that causes malaria and the immune system that enables the parasite to persist in an otherwise functional immune system. A close second is the antigenic targets in malaria and how to overcome the enormous polymorphism of these targets. Meeting these challenges represents a call to arms of basic immunologists to advance our knowledge of malaria immunity.