Human antibodies to recombinant protein constructs of Plasmodium falciparum Apical Membrane Antigen 1 (AMA1) and their associations with protection from malaria

被引:167
作者
Polley, SD
Mwangi, T
Kocken, CHM
Thomas, AW
Dutta, S
Lanar, DE
Remarque, E
Ross, A
Williams, TN
Mwambingu, G
Lowe, B
Conway, DJ
Marsh, K
机构
[1] Univ London London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London WC1E 7HT, England
[2] Ctr Geog Med Res, Kenya Med Res Inst, Coast Wellcome Trust Collaborat Program, Kilifi, Kenya
[3] BPRC, Dept Parasitol, NL-2280 GH Rijswijk, Netherlands
[4] Walter Reed Army Inst Res, Dept Immunol, Silver Spring, MD 20910 USA
[5] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Med, Ctr Trop Med, Oxford OX3 9DY, England
[6] Swiss Trop Inst, Dept Epidemiol & Publ Hlth, CH-4003 Basel, Switzerland
基金
英国医学研究理事会; 英国惠康基金;
关键词
Kenya; merozoite; epidemiology; allele specificity; subclass;
D O I
10.1016/j.vaccine.2004.05.031
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Serum antibodies from 1071 people in two Kenyan villages were assayed using eight different recombinant Apical Membrane Antigen I (AMA1) protein constructs to investigate their role in naturally acquired immunity. In both communities, antibodies against the full-length ectodomain (both FVO and 3D7 allele Constructs) prior to a malaria transmission season were significantly associated with protection front malaria in the following 6 months. even after adjusting for age and antibody reactivity to whole parasite (schizont) extract. However, these protective associations of antibodies were only seen among subjects that were parasite slide positive at the time of pre-season serum sampling. Competition ELISAs with the FVO and 3D7 allele constructs showed that antibodies can recognise either conserved or allele-specific epitopes in AMA1. Results encourage the development of an AMA1 vaccine based on the full-length ectodomain. and indicate that the function of human antibodies to allele-specific and conserved epitopes in AMA1 should be studied further. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码:718 / 728
页数:11
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