TABLE 1

Challenges in developing malaria vaccines based on in vitro chemical attenuation

ChallengeSolution
Underattenuation of parasitesIn vitro assessment and preclinical studies can provide preliminary data on the amount of the chemical required to adequately attenuate the parasite. However, this needs to be confirmed by rigorous assessment in pilot studies and phase I safety trials in humans.
Use of human blood in chemically attenuated blood-stage vaccines and the possible induction of antibodies against red blood cell surface antigens (ABO and Rh blood group systems)This can be greatly limited by the use of red blood cells from universal donors (blood group O Rh negative). Additionally, antibodies to minor antigens can be addressed by limiting the number of uninfected red cells in the vaccine.
Storage and deployment of vaccineCryopreservation of the vaccine is likely to be required. Methods for cryopreserving unattenuated sporozoites and blood-stage parasites, as well as irradiation-attenuated sporozoites, have been established (46, 47). These methods may be applicable to the cryopreservation of in vitro chemically attenuated sporozoites and blood-stage parasites.