Characterization of Naturally Acquired Antibodies to the non-Repetitive Flanking Regions of the Circumsporozoite Protein of Plasmodium Falciparum

Arthur E. BrownArmed Forces Research Institute for Medical Sciences, Walter Reed Army Institute of Research, SmithKline Beecham Pharmaceuticals, Bangkok, Thailand

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H. Kyle WebsterArmed Forces Research Institute for Medical Sciences, Walter Reed Army Institute of Research, SmithKline Beecham Pharmaceuticals, Bangkok, Thailand

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Daniel M. GordonArmed Forces Research Institute for Medical Sciences, Walter Reed Army Institute of Research, SmithKline Beecham Pharmaceuticals, Bangkok, Thailand

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Barnyen PermpanichArmed Forces Research Institute for Medical Sciences, Walter Reed Army Institute of Research, SmithKline Beecham Pharmaceuticals, Bangkok, Thailand

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Mitchell GrossArmed Forces Research Institute for Medical Sciences, Walter Reed Army Institute of Research, SmithKline Beecham Pharmaceuticals, Bangkok, Thailand

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Antibody responses to the circumsporozoite (CS) protein of Plasmodium falciparum have previously been reported against the central repeating tetrapeptides of this protein. Segments of the protein flanking the repeat region also contain B-cell epitopes, but specific antibody responses have not been previously characterized. Longitudinal serum sets from 16 Thai adults who developed acute falciparum malaria were selected to represent a spectrum of antibody response to the repeat region (R32). These sera were assayed by enzyme-linked immunosorbent assay using as capture antigen a recombinant fusion protein, NS181RLF, which contains both flanking regions, but lacks the NANP and NVDP repeats of the P. falciparum CS protein. Antibody responses to the repeatless flanking (RLF) regions were observed in all subjects, including five individuals who lacked detectable anti-R32 antibody responses. Anti-RLF antibody responses induced by natural infection appear to be short-lived and of low-to-moderate magnitude. Thus, if anti-RLF antibodies prove to be protective, derived vaccine candidates may require presentation of these epitopes with adjuvants or delivery systems that enhance immunogenicity.

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