Credit: Pr. Bouree / Photo Researchers, Inc.

Malaria kills one million individuals each year, and half the world's population is at risk of infection. Yet there exists no effective vaccine for this disease. Two recent clinical studies of candidate malaria vaccines reflect the ongoing challenges to developing a protective vaccine (Science doi:10.1126/science.1211548, 8 September; N. Engl. J. Med. 365, 1004–1013).

Epstein et al. tested in humans the protective efficacy of a vaccine comprised of live attenuated but nonreplicating Plasmodium falciparum sporozoites injected subcutaneously or intradermally. But of 44 immunized individuals, only two were protected against challenge with P. falciparum–infected mosquitoes. However, intravenous injection of a similar vaccine in mice protected 71–100% of mice from challenge with the mouse parasite Plasmodium yoelii. The authors suggest that the route of administration may be crucial to the efficacy of their vaccine, and a further clinical trial will test this hypothesis in humans by assessing protection conferred by intravenous injection.

Whereas Epstein et al. tested whether the whole parasite could induce protection against infection, Thera et al. reported the results of a double-blind randomized trial of a subunit—or protein—vaccine designed to reduce the clinical severity caused by Plasmodium infection of red blood cells. But of 400 children immunized with this vaccine or a control rabies vaccine, only 17.4% of the recipients of the subunit vaccine were protected from clinical malaria at 6 months.

The malaria life cycle is extremely complex, and the mechanisms required for vaccine-induced protective immunity in humans remain unclear. Although clinical trials of one vaccine candidate—RTS,S—are quite advanced and the results are promising, protection from infection is not complete, and development of additional vaccine candidates that elicit significant protection and can be feasibly administered to at-risk populations is essential.