title: Influence of immunoadjuvants and a promiscous T-cell determinant on the immunogenicity of RESA peptide antigen of P. falciparum.
abstract: Synthetic peptide antigens representing the repeat sequences of malarial antigens showed poor immunogenicity and protection in clinical trials. In the present study, RESA, an asexual blood stage antigen, containing (EENVEHDA)2 and (DDEHVEEPTVA)2 sequences were chemically linked to a promiscous T-cell determinant (CS.T3) of the circumsporozoite protein of P. falciparum. The synthetic constructs either alone or coentrapped with immunoadjuvants (nor muramyl dipeptide/lauroyl tetrapeptide) were administered in liposomes to mice of varying genetic background and the immunogenicity of different formulations were compared under identical experimental conditions. The RESA peptide formulations containing the T-cell determinant and the adjuvants generated high titre and affinity antibodies in all the strains, as compared to peptide(s) alone. The booster immunization induced a strong anamnestic response in each group. Though the major IgG isotype is of IgG1 and IgG2b interestingly, formulations containing CS.T3 have a higher proportion of cytophilic IgG2b isotype. There was a significant fall in the levels of IgG2b isotype while IgG1 levels were maintained same in the third bleed (day 60, without booster immunization). The mixed peptide group preparation containing the adjuvant is found to be a better immunogen than that of respective peptides itself. The in vitro merozoite reinvasion inhibition assay showed 76-96% inhibition with the formulations containing RESA peptide(s)-CS.T3 and the adjuvant, while with peptides alone the inhibition was 50-56%. This study highlights the importance of an alternative approach for developing peptide based immunogen against malaria.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi.
authors.forename: B
authors.initials: B
authors.lastname: Chaba
authors.forename: P
authors.initials: P
authors.lastname: Kumar
authors.forename: W
authors.initials: W
authors.lastname: Haq
authors.forename: L
authors.initials: L
authors.lastname: Sabhnani
authors.forename: D N
authors.initials: DN
authors.lastname: Rao
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000494:pharmacology*; D005260:Female; D007117:Immunization, Secondary; D018796:Immunoconjugates / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D018984:Epitopes, T-Lymphocyte; D018796:Immunoconjugates; D008081:Liposomes; D015800:Protozoan Proteins; C050256:ring-infected erythrocyte surface antigen (RESA), Plasmodium falciparum; D000119:Acetylmuramyl-Alanyl-Isoglutamine