SAFETY, IMMUNOGENICITY, AND EFFICACY OF A RECOMBINANTLY PRODUCED PLASMODIUM-FALCIPARUM CIRCUMSPOROZOITE-PROTEIN HEPATITIS-B SURFACE-ANTIGENSUBUNIT VACCINE

Twenty malaria-naive volunteers received a recombinant Plasmodium falc iparum malaria vaccine (RTS,S) containing 19 NANP repeats and the carb oxy terminus (amino acids 210-398) of the circumsporozoite (CS) antige n coexpressed in yeast with hepatitis B surface antigen, Ten received vaccine adjuvanted with alum, and 10 received vaccine adjuvanted with alum plus 3-deacylated monophosphoryl lipid A (MPL). Both formulations were well tolerated and immunogenic. MPL enhanced CS antibody levels (measured by ELISA, immunofluorescence, and inhibition of sporozoite i nvasion assays). After sporozoite challenge, 6 of 6 in the alum group and 6 of 8 in the alum-MPL group developed patent malaria. Protected s ubjects had higher levels of C'S antibody titers on day of challenge t han did nonprotected subjects. After immunization, 1 protected subject had increased cytotoxic T lymphocyte activity against CS and recall o f memory T cell responses to RTS,S and selected CS.