REGULATION OF ANTIBODY SPECIFICITY TO PLASMODIUM-FALCIPARUM MEROZOITESURFACE PROTEIN-1 BY ADJUVANT AND MHC HALOTYPE

An effective malaria vaccine must be capable of eliciting a protective immune response in individuals of diverse genetic makeup. In this rep ort, we describe the co-regulation of immune responsiveness to growth- inhibitory Plasmodium falciparum merozoite surface protein-1 (MSP-1) e pitopes by MHC-linked immune response genes and by the adjuvant used i n MSP-1 vaccine formulations. When congenic mice differing in MHC hapl otype were immunized with MSP-1 either in CFA or incorporated into a s ynthetic monophosphoryl lipid A (LA-15-PH)-liposome formulation, mice of different haplotypes produced anti-MSP-1 Abs capable of inhibiting P. falciparum growth. Mice of H-2(b) and H-2(ja) haplotypes produced A bs possessing high levels of inhibitory activity upon immunization wit h MSP-1 in LA-15-PH/liposomes whereas these haplotypes produced noninh ibitory Abs when immunized with MSP-1 in CFA. Conversely, H-2(d) haplo type mice produced inhibitory Abs when immunized with MSP-1 in CFA but not when immunized with MSP-1 in LA-15-PH/liposomes. The LA-15-PH/lip osome adjuvant was more effective than CFA in inducing growth-inhibito ry Abs. The level of parasite growth inhibition observed for a particu lar mouse strain correlated with Ah titers against conserved, C-termin al MSP-1 epitopes, which appear to be important targets for Ab-mediate d inhibition in mice immunized with both adjuvant formulations. Our re sults suggest that adjuvant formulation and MHC genes act in a recipro cal manner to control immune responsiveness to specific epitopes, and raise the possibility of manipulating genetically-controlled responsiv eness to vaccine Ags by utilizing alternative adjuvants in vaccine for mulations.