Abstract: Transcript profiles for irradiated and non-irradiated P. falciparum sporozoites were compared in an attempt to identify transcripts that are reproducibly perturbed by irradiation. Four loci were identified with high confidence. Three of these transcripts were derived from 3 different known gene families, and the fourth from a gene encoding a conserved hypothetical protein of unknown function. All four loci are up-regulated in radiation attenuated sporozoites which have been shown to be very effective in establishing protective immunity against malaria. Up-regulation of these transcripts contributes directly to protective immunity. The polypeptides encoded by the transcripts, individually and/or in combination, are incorporated into subunit vaccines, useful for the prevention of malaria and the establishment of protective immunity against malaria.