Regulation of antibody specificity to Plasmodium falciparum merozoite surface protein-1 by adjuvant and MHC haplotype

Abstract

An effective malaria vaccine must be capable of eliciting a protective immune response in individuals of diverse genetic makeup. In this report, we describe the co-regulation of immune responsiveness to growth-inhibitory Plasmodium falciparum merozoite surface protein-1 (MSP-1) epitopes by MHC-linked immune response genes and by the adjuvant used in MSP-1 vaccine formulations. When congenic mice differing in MHC haplotype were immunized with MSP-1 either in CFA or incorporated into a synthetic 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-2b and H-2ja haplotypes produced Abs possessing high levels of inhibitory activity upon immunization with MSP-1 in LA-15-PH/liposomes whereas these haplotypes produced noninhibitory Abs when immunized with MSP-1 in CFA. Conversely, H-2d haplotype 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/liposome adjuvant was more effective than CFA in inducing growth-inhibitory Abs. The level of parasite growth inhibition observed for a particular mouse strain correlated with Ab titers against conserved, C-terminal MSP-1 epitopes, which appear to be important targets for Ab-mediated inhibition in mice immunized with both adjuvant formulations. Our results suggest that adjuvant formulation and MHC genes act in a reciprocal manner to control immune responsiveness to specific epitopes, and raise the possibility of manipulating genetically-controlled responsiveness to vaccine Ags by utilizing alternative adjuvants in vaccine formulations.