Asexual blood-stage malaria vaccine development: facing the challenges

The aim of this article is to highlight the challenges that researchers face in the development of asexual blood-stage vaccines, and the progress made recently towards achieving the goal of a successful candidate to reduce morbidity.There is good rationale to support the development of blood-stage malaria vaccines, the most promising being the demonstration that nonimmune volunteers repeatedly challenged and cured with blood-stage parasites developed immunity to subsequent challenge as well as the demonstration of the efficacy of the first asexual blood-stage vaccine tested in a malaria endemic area (combination B) to reduce parasite density in children. The selective pressure induced by this vaccine and the accumulating evidence of extensive antigenic diversity of blood-stage proteins pose a difficult challenge to vaccine researchers. Numerous clinical trials, both in nonendemic and endemic areas, are being conducted with different antigens, different allelic types and different protein fragments.Considerable efforts and funding are available to shift from laboratory experiments to field trials. Field trials remain the definitive method to assess the real impact of different vaccines in the target populations. More rigorous side-by-side comparisons are needed between the different vaccines using standardized in-vitro and in-vivo testing, so that the most promising candidates will be selected for further development.