SAFETY, IMMUNOGENICITY, AND EFFICACY OF A MALARIA SPOROZOITE VACCINE ADMINISTERED WITH MONOPHOSPHORYL LIPID A, CELL-WALL SKELETON OF MYCOBACTERIA, AND SQUALANE AS ADJUVANT

A Plasmodium falciparum circumsporozoite protein (PfCSP) recombinant f usion protein, R32NS1(81), formulated with monophosphoryl lipid A, cel l wall skeleton of mycobacteria, and squalane (Detox(TM)) was administ ered to 12 volunteers. One volunteer had malaise and self-limited pain ful induration at the injection site after the second dose and decline d further immunization. The other 11 volunteers tolerated the three do ses of 1,230 mu g of vaccine, but most complained of sore arms; in fiv e cases the pain or malaise was severe enough to interfere with work o r sleep. Two weeks after the third dose of vaccine, four of the 11 imm unized volunteers had greater than or equal to 14 mu g/ml of antibodie s to the repeat region of the PfCSP in their serum. Two of these four volunteers did not develop P. falciparum parasitemia when challenged b y the bite of five mosquitoes carrying P. falciparum sporozoites. The seven volunteers with lower levels of antibodies and 11 of 11 controls developed parasitemia. These data are consistent with other studies, and indicate that vaccine-induced antibodies against the repeat region of PfCSP can prevent effective sporozoite infection of hepatocytes in humans. The challenge is to improve the immunogenicity of PfCSP-based vaccines, and to develop methods for including PfCSP peptides as comp onents of multitarget malaria vaccines.