Identification of a major B-cell epitope of the Plasmodium falciparum glutamate-rich protein (GLURP), targeted by human antibodies mediating parasitekilling

The antigenicity of the glutamate-rich protein (GLURP) of Plasmodium falcip arum was comprehensively evaluated in epitope-mapping studies utilizing a p hage display library, synthetic peptides and anti-GLURP IgG preparations pr eviously shown to promote strong antibody-dependent cellular inhibition (AD CI) effects. We identified six major B-cell epitopes within the nonrepetiti ve region RO, corresponding to amino acid residues 173 to 187 (P1), 193 to 207 (P3), 216 to 229 (P4), 264 to 288 (P11), 343 to 357 (P10), and 407 to 4 34 (S3). Of these, four (P1, P3, P4, and S3) were frequently recognized by high-titered Ige antibodies in plasma samples from immune Liberian adults ( prevalence: 29.1-45.0%). The three epitopes P1, P3, and P4 contained a comm on motif (seven out of nine positions are identical) and may thus constitut e a family of structurally related epitopes. This leaves two distinct epito pes, one (P3) representing this new epitope family and S3 as targets for bi ologically active antibodies. Human IgG antibodies from single plasma sampl es were affinity-purified against these peptides. P3-specific IgG preparati ons were consistently more effective in ADCI than S3-specific Igc. Among th e different GLURP epitopes, we therefore suggest that the P3 epitope is pot entially the most important epitope in GLURP for the development of clinica l immunity to malaria in man. (C) 2000 Elsevier Science Ltd. All rights res erved.