Longitudinal analyses of immune responses to Plasmodium falciparum derived peptides corresponding to novel blood stage antigens in coastal Kenya


Agak, GW; Bejon, P; Fegan, G; Gicheru, N; Villard, V; Kajava, AV; Marsh, K; Corradin, G; (2008) Longitudinal analyses of immune responses to Plasmodium falciparum derived peptides corresponding to novel blood stage antigens in coastal Kenya. Vaccine, 26 (16). pp. 1963-1971. ISSN 0264-410X DOI: https://doi.org/10.1016/j.vaccine.2008.02.020

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Abstract

We have recently described 95 predicted alpha-helical coiled-coil peptides derived from putative Plasmodium falciparum erythrocytic stage proteins. Seventy peptides recognized with the highest level of prevalence by sera from three endemic areas were selected for further studies. In this study, we sequentiatty examined antibody responses to these synthetic peptides in two cohorts of children at risk of clinical, mataria in Kilifi district in coastal Kenya, in order to characterize the level of peptide recognition by age, and the role of antipeptide antibodies in protection from clinical malaria. Antibody levels from 268 children in the first cohort (Chonyi) were assayed against 70 peptides. Thirty-nine peptides were selected for further study in a second cohort (Junju). The rationale for the second cohort was to confirm those peptides identified as protective in the first cohort. The Junju cohort comprised of children aged 1-6 years old (inclusive). Children were actively followed up to identify episodes of febrile malaria in both cohorts. Of the 70 peptides examined, 32 showed significantly (p < 0.05) increased antibody recognition in older children and 40 showed significantly increased antibody recognition in parasitaemic children. Ten peptides were associated with a significantly reduced odds ratio (OR) for an episode of clinical malaria in the first cohort of children and two of these peptides (LR146 and AS202.11) were associated with a significantly reduced OR in both cohorts. LR146 is derived from hypothetical protein PFBO145c in PlasmoDB. Previous work has identified this protein as a target of antibodies effective in antibody dependent cellular inhibition (ADCI). The current Study substantiates further the potential of protein PFBO145c and also identifies protein PF11_0424 as another likely target of protective antibodies against P falciparum malaria. (c) 2008 Elsevier Ltd. All rights reserved.

Item Type: Article
Keywords: hypothetical malaria proteins, alpha-helical coiled-coil domains, peptides, genome, GLUTAMATE-RICH PROTEIN, ERYTHROCYTE SURFACE-ANTIGENS, NEW-GUINEAN, CHILDREN, CLINICAL MALARIA, ANTIBODY-RESPONSES, CIRCUMSPOROZOITE, PROTEIN, ACQUIRED-IMMUNITY, SERUM ANTIBODIES, ME-TRAP, PROTECTION
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Research Centre: Tropical Epidemiology Group
PubMed ID: 18342997
Web of Science ID: 255267300007
URI: http://researchonline.lshtm.ac.uk/id/eprint/7612

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