Inducing protective antibodies against ring-infected erythrocyte surface peptide antigen of Plasmodium falciparum using immunostimulating complex (ISCOMs) delivery

Abstract

In the present study, synthetic peptides (EENVEHDA)₂ [(oc)₂] and (DDEHVEEPTVA)₂ [(un)₂] of ring-infected erythrocyte surface antigen (RESA) of Plasmodium falciparum were linked with palmitic acid and entrapped in immunostimulating complexes (ISCOMs). The immunogenicity of the peptide(s) and mixture of peptides were studied in mice with different genetic background. Peptide(s) entrapped in ISCOMs using a low-dose immunization strategy generated high-titer as well as high-affinity antibodies. Interestingly, no genetic restriction of the immune response was observed in any of the strains studied. The IgG subclass pattern with the peptide(s) showed predominately IgG2a/2b isotypes, while with the mixed peptide formulation, (un)₂-specific IgG isotype pattern showed induction of both IgG1 and IgG2a/2b isotypes. These cytophilic antibodies inhibited the ring as well as schizont stage and total parasite growth during in vitro merozoite reinvasion inhibition study. In the mixed peptide preparation, the same pattern of immune response was achieved as that of individual peptide(s) using ISCOMs delivery. Therefore, the entrapment of otherwise poorly immunogenic synthetic peptides in ISCOMs resulted in increased immunogenicity followed by strong secondary response and can be adopted for developing subunit immunogen formulation against malarial parasite.