Selection of glutamate-rich protein long synthetic peptides for vaccine development: Antigenicity and relationship with clinical protection and immunogenicity

Antibodies against three long synthetic peptides (LSPs) derived from the gl utamate-rich protein (GLURP) of Plasmodium falciparum were analyzed in thre e cohorts from Liberia, Ghana, and Senegal. Two overlapping LSPs, LR67 and LR68, are derived from the relatively conserved N-terminal nonrepeat region (R0), and the third, LR70, is derived from the R2 repeat region. A high pr evalence of antibody responses to each LSP was observed in all three areas of endemic infection. Levels of cytophilic immunoglobulin G (IgG) antibodie s against both GLURP regions were significantly correlated with protection from clinical P. falciparum malaria. Protected children from the Ghana coho rt possessed predominantly IgG1 antibodies against the nonrepeat epitope an d IgG3 antibodies against the repeat epitope. T-cell proliferation response s, studied in the cohort from Senegal, revealed that T-helper-cell epitopes were confined to the nonrepeat region. When used as immunogens, the LR67 a nd LR68 peptides elicited strong IgG responses in outbred mice and LR67 als o induced antibodies in mice of different H-2 haplotypes, confirming the pr esence of T-helper-cell epitopes in these constructs. Mouse antipeptide ant isera recognized parasite proteins as determined by immunofluorescence and immunoblotting. This indicates that synthetic peptides derived from relativ ely conserved epitopes of GLURP might serve as useful immunogens for vaccin ation against P. falciparum malaria.