title: Protection of Malian children from clinical malaria is associated with recognition of multiple antigens.
abstract: BACKGROUND
  Naturally acquired immunity to clinical malaria is thought to be mainly antibody-mediated, but reports on antigen targets are contradictory. Recognition of multiple antigens may be crucial for protection. In this study, the magnitude of antibody responses and their temporal stability was assessed for a panel of malaria antigens in relation to protection against clinical Plasmodium falciparum malaria.
  
  
  METHODS
  Malian children aged two to 14 years were enrolled in a longitudinal study and followed up by passive and active case detection for seven months. Plasma was collected at enrolment and at the beginning, in the middle and after the end of the transmission season. Antibody titres to the P. falciparum-antigens apical membrane protein (AMA)-1, merozoite surface protein (MSP)-1₁₉, MSP-3, glutamine-rich protein (GLURP-R0) and circumsporozoite antigen (CSP) were assessed by enzyme-linked immunosorbent assay (ELISA) for 99 children with plasma available at all time points. Parasite carriage was determined by microscopy and nested PCR.
  
  
  RESULTS
  Antibody titres to all antigens, except MSP-1₁₉, and the number of antigens recognized increased with age. After malaria exposure, antibody titres increased in children that had low titres at baseline, but decreased in those with high baseline responses. No significant differences were found between antibody titers for individual antigens between children remaining symptomatic or asymptomatic after exposure, after adjustment for age. Instead, children remaining asymptomatic following parasite exposure had a broader repertoire of antigen recognition.
  
  
  CONCLUSIONS
  The present study provides immune-epidemiological evidence from a limited cohort of Malian children that strong recognition of multiple antigens, rather than antibody titres for individual antigens, is associated with protection from clinical malaria.
authors: Department of Epidemiology of Parasitic Diseases, Malaria Research and Training Centre, University of Science, Techniques and Technologies of Bamako, Bamako, Mali. van@icermali.org.|Department of Medical Microbiology, Radboud university medical center, Route 268, PO Box 9101, 6500, HB Nijmegen, The Netherlands. van@icermali.org.
authors: Modibo
authors: M
authors: Daou
authors: Department of Epidemiology of Parasitic Diseases, Malaria Research and Training Centre, University of Science, Techniques and Technologies of Bamako, Bamako, Mali. kouriba@icermali.org.
authors: Bourèma
authors: B
authors: Kouriba
authors: Centre National de Recherche et de Formation sur le Paludisme (CNRFP), Ouagadougou, Burkina Faso. o.nicolas.cnrfp@fasonet.bf.
authors: Nicolas
authors: N
authors: Ouédraogo
authors: Department of Epidemiology of Parasitic Diseases, Malaria Research and Training Centre, University of Science, Techniques and Technologies of Bamako, Bamako, Mali. idiarra@icermali.org.
authors: Issa
authors: I
authors: Diarra
authors: Department of Epidemiology of Parasitic Diseases, Malaria Research and Training Centre, University of Science, Techniques and Technologies of Bamako, Bamako, Mali. charama@icermali.org.
authors: Charles
authors: C
authors: Arama
authors: Department of Epidemiology of Parasitic Diseases, Malaria Research and Training Centre, University of Science, Techniques and Technologies of Bamako, Bamako, Mali. yamoussak@icermali.org.
authors: Yamoussa
authors: Y
authors: Keita
authors: Department of Epidemiology of Parasitic Diseases, Malaria Research and Training Centre, University of Science, Techniques and Technologies of Bamako, Bamako, Mali. sisissoko@yahoo.fr.
authors: Sibiri
authors: S
authors: Sissoko
authors: Department of Epidemiology of Parasitic Diseases, Malaria Research and Training Centre, University of Science, Techniques and Technologies of Bamako, Bamako, Mali. boucary2008@yahoo.fr.
authors: Boucary
authors: B
authors: Ouologuem
authors: Department of Epidemiology of Parasitic Diseases, Malaria Research and Training Centre, University of Science, Techniques and Technologies of Bamako, Bamako, Mali. seydou@icermali.org.
authors: Seydou
authors: S
authors: Arama
authors: Department of Medical Microbiology, Radboud university medical center, Route 268, PO Box 9101, 6500, HB Nijmegen, The Netherlands. Teun.Bousema@radboudumc.nl.|Department of Infection and Immunity, London School of Hygiene and Tropical Medicine, London, UK. Teun.Bousema@radboudumc.nl.
authors: Teun
authors: T
authors: Bousema
authors: Department of Epidemiology of Parasitic Diseases, Malaria Research and Training Centre, University of Science, Techniques and Technologies of Bamako, Bamako, Mali. okd@icermali.org.
authors: Ogobara K
authors: OK
authors: Doumbo
authors: Department of Medical Microbiology, Radboud university medical center, Route 268, PO Box 9101, 6500, HB Nijmegen, The Netherlands. robert.sauerwein@radboudumc.nl.
authors: Robert W
authors: RW
authors: Sauerwein
authors: Department of Medical Microbiology, Radboud university medical center, Route 268, PO Box 9101, 6500, HB Nijmegen, The Netherlands. anja.scholzen@radboudumc.nl.
authors: Anja
authors: A
authors: Scholzen
mesh_terms: D000293:Adolescent; D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000276:immunology*; D008302:Mali / Q000453:epidemiology; D012621:Seasons
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan
references: Cytometry A. 2007 Apr;71(4):242-50
references: 17252581
references: PLoS One. 2012;7(12):e52939
references: 23300828
references: Malar J. 2012;11:29
references: 22289302
references: Vaccine. 2013 Aug 20;31(37):3936-42
references: 23800539
references: Bull Soc Pathol Exot. 2003 Nov;96(4):308-12
references: 14717049
references: Infect Immun. 2008 May;76(5):2240-8
references: 18316390
references: Parasite Immunol. 2013 May-Jun;35(5-6):164-73
references: 23473542
references: Infect Immun. 2002 Aug;70(8):4471-6
references: 12117958
references: Infect Immun. 2013 Oct;81(10):3586-99
references: 23836827
references: Lancet. 2010 Nov 6;376(9752):1566-78
references: 21035842
references: Malar J. 2008;7:142
references: 18664257
references: Mol Cell Proteomics. 2011 Sep;10(9):M111.007948
references: 21628511
references: Proc Natl Acad Sci U S A. 2012 May 22;109(21):8247-52
references: 22566630
references: Infect Immun. 2009 May;77(5):1917-23
references: 19223480
references: Vaccine. 2008 Nov 11;26(48):6143-50
references: 18804135
references: Trans R Soc Trop Med Hyg. 1993 Nov-Dec;87(6):649-53
references: 8296364
references: Int J Parasitol. 2012 May 15;42(6):535-48
references: 22561398
references: Epidemics. 2011 Jun;3(2):109-18
references: 21624782
references: Proc Natl Acad Sci U S A. 2010 Apr 13;107(15):6958-63
references: 20351286
references: J Infect Dis. 2007 Jan 15;195(2):279-87
references: 17191173
references: Malar J. 2009;8:63
references: 19366448
references: Science. 1987 Aug 7;237(4815):639-42
references: 3299709
references: Mol Biochem Parasitol. 1994 Mar;64(1):165-9
references: 8078519
references: Cell. 2007 Nov 2;131(3):492-504
references: 17981117
references: Malar J. 2009;8:242
references: 19860926
references: Am J Trop Med Hyg. 1991 Sep;45(3):297-308
references: 1928564
references: Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):305-10
references: 18172196
references: Mol Biochem Parasitol. 1991 Nov;49(1):119-31
references: 1775153
references: Am J Trop Med Hyg. 1989 Apr;40(4):351-5
references: 2469336
references: Annu Rev Immunol. 2005;23:367-86
references: 15771575
references: J Biol Chem. 2004 Mar 5;279(10):9490-6
references: 14676185
references: N Engl J Med. 2008 Dec 11;359(24):2533-44
references: 19064623
references: J Exp Med. 1988 Jan 1;167(1):231-6
references: 3275737
references: PLoS Pathog. 2010 May;6(5):e1000912
references: 20502681
references: J Infect Dis. 1996 Mar;173(3):765-9
references: 8627050
references: Blood. 1994 Sep 1;84(5):1594-602
references: 8068948
references: Nat Commun. 2012;3:1237
references: 23212366
references: Nat Rev Microbiol. 2014 Dec;12(12):833-40
references: 25329408
references: Parasite Immunol. 2004 Jun-Jul;26(6-7):265-72
references: 15541030
references: PLoS One. 2008;3(2):e1570
references: 18270564
references: Am J Trop Med Hyg. 1983 Jan;32(1):24-30
references: 6337518
references: Infect Immun. 2002 Nov;70(11):6075-82
references: 12379684
references: Malar J. 2012;11:427
references: 23259607
references: N Engl J Med. 2014 May 8;370(19):1799-808
references: 24806160
references: PLoS Med. 2010 Jan;7(1):e1000218
references: 20098724
references: Sci Transl Med. 2014 Jul 30;6(247):247ra102
references: 25080477
references: Biotechniques. 1991 Apr;10(4):506-13
references: 1867860
references: Malar J. 2007;6:82
references: 17598897
references: N Engl J Med. 2008 Dec 11;359(24):2521-32
references: 19064627
references: Trop Med Int Health. 2004 Aug;9(8):862-8
references: 15303990
references: J Clin Invest. 2012 Oct;122(10):3618-28
references: 22996664
references: Parasitol Today. 1994 Nov;10(11):439-42
references: 15275531
references: Am J Trop Med Hyg. 1999 Mar;60(3):357-63
references: 10466961
references: Malar J. 2012;11:11
references: 22230255
references: Nature. 1961 Nov 25;192:733-7
references: 13880318
references: Am J Trop Med Hyg. 2005 Jul;73(1):222-8
references: 16014863
references: N Engl J Med. 2009 Jul 30;361(5):468-77
references: 19641203
references: J Immunol Methods. 2012 Oct 31;384(1-2):62-70
references: 22835432
references: J Infect Dis. 2004 Nov 1;190(9):1527-33
references: 15478055
references: Lancet Infect Dis. 2011 Feb;11(2):102-9
references: 21237715
references: Vaccine. 2007 Apr 12;25(15):2930-40
references: 16914240