A biologist's perspective on malaria vaccine development.

A vaccine to reduce human suffering caused by malarial parasites has been the holy grail of malaria research. Early studies in the 1940s indicated that attenuated parasites could induce useful immunity. Since that time the genomic revolution led inevitably to the idea of cheap production of safe recombinant vaccines using either expressed protein or DNA vector technologies. It has been difficult to reflect with these 'simple' formulations the efficacies observed with intact parasite immunogens. With the new-found ability to attenuate the parasites by genetic manipulation, ideas have come full circle. Some of the highs and lows of this journey are described from the specific viewpoint of our growing understanding of parasite biology. The objective of many current vaccine initiatives targeting morbidity and mortality is questioned in the light of renewed calls to consider eradication as an objective. The biological rational for approaches to limit parasite transmission are highlighted and their place in future efforts to improve the lives of the 40% of the world's population at risk of the disease is discussed.