The Development of Molecular Vaccines against Malaria Sporozoites

Abstract

The successful development of an efficacious molecular vaccine against malaria has long been a major research goal of the Walter Reed Army Institute of Research, the World Health Organization and major international public health agencies. Although this goal has not yet been achieved, immense progress has been made in the area of sporozoite vaccines since the gene encoding the Plasmodium falciparum circumsporozoite (CS) protein was cloned and sequenced in 1984 (Dame et al., 1984). The basis for a subunit approach to sporozoite immunity was established in the early 1970’s in a series of landmark studies demonstrating that mice, primates, and humans could be protected against sporozoite challenge by immunization with radiation-attenuated sporozoites (Nussenzweig et al. 1969; Clyde et al., 1975; Rieckman et al., 1979). These studies demonstrated that protective immunity was species and stage specific, but since large numbers of sporozoites were required for its induction, it was not feasible to develop live attenuated sporozoite vaccines for general use. Moreover, the mechanism of immunity to irradiated sporozoites is complex, and includes the induction of both humoral and cellular immune responses.