Synthetic malaria peptide vaccine elicits high levels of antibodies in vaccinees of defined HLA genotypes

A multiple antigen peptide (MAP) malaria vaccine containing minimal Plasmod ium falciparum circumsporozoite protein repeat epitopes was assessed for sa fety and immunogenicity in volunteers of known class II genotypes. The MAP/ alum/QS-21 vaccine formulation elicited high levels of parasite-specific an tibodies in 10 of 12 volunteers expressing DQB1*0603, DRB1*0401, or DRB1*11 01 class II molecules. In contrast, volunteers of other HLA genotypes were low responders or nonresponders. A second study of 7 volunteers confirmed t he correlation of class II genotype and high responder phenotype. This is t he first demonstration in humans that a peptide vaccine containing minimal T and B cell epitopes composed of only 5 amino acids (N, A, V, D, and P) ca n elicit antibody titers comparable to multiple exposures to irradiated P f alciparum-infected mosquitoes. Moreover, the high-responder phenotypes were predicted by analysis of peptide/HLA interactions in vitro, thus facilitat ing the rational design of epitope-based peptide vaccines for malaria, as w ell as for other pathogens.