ABSTRACT
The potential benefit of a vaccine is matched only by the difficulties facing those trying to develop it (32). Expertly adapted to surviving long term in its hostb, the parasite evades or manipulates to its advantage the host immune response, the very tool that scientists must use to suppress or eliminate the infection (36-44). As a pathogen, it is exceedingly complex, with a multistage life cycle characterized by stage-specific expression of proteins (45) and a bewildering choice of 5300 genes that could be selected as components of a vaccine (46). This diversity is augmented by the often extensive polymorphisms of candidate antigens (47), which may induce allelespecific immune responses unable to provide cross-protection against the diverse genotypes encountered in the field (48). After decades of development, the leading vaccine candidate, RTS,S, projected for licensure in the next four to five years (49), appears unlikely to significantly reduce the prevalence of infection, although it stands a reasonable chance to offer a degree of protection against clinical illness (50). Perseverance and possibly a measure of good fortune will be needed to realize the dream shared by so many to provide this one critical tool in the struggle for world health.
