title: Immune mechanisms in malaria: new insights in vaccine development.
abstract: Early data emerging from the first phase 3 trial of a malaria vaccine are raising hopes that a licensed vaccine will soon be available for use in endemic countries, but given the relatively low efficacy of the vaccine, this needs to be seen as a major step forward on the road to a malaria vaccine rather than as arrival at the final destination. The focus for vaccine developers now moves to the next generation of malaria vaccines, but it is not yet clear what characteristics these new vaccines should have or how they can be evaluated. Here we briefly review the epidemiological and immunological requirements for malaria vaccines and the recent history of malaria vaccine development and then put forward a manifesto for future research in this area. We argue that rational design of more effective malaria vaccines will be accelerated by a better understanding of the immune effector mechanisms involved in parasite regulation, control and elimination.
authors: Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. eleanor.riley@lshtm.ac.uk
authors: Eleanor M
authors: EM
authors: Riley
authors: V Ann
authors: VA
authors: Stewart
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D014644:Genetic Variation; D006801:Humans; D008018:Life Cycle Stages; D008288:Malaria / Q000276:immunology*; D017780:Malaria Vaccines / Q000276:immunology*; D010961:Plasmodium / Q000235:genetics / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination
chemical_list: D017780:Malaria Vaccines
references: Nature. 2006 Feb 23;439(7079):1004-8
references: 16382237
references: Nat Immunol. 2011 Jul 10;12(8):786-95
references: 21743478
references: Eur J Immunol. 2009 Nov;39(11):3042-51
references: 19658096
references: Infect Immun. 2002 Sep;70(9):5328-31
references: 12183594
references: Infect Immun. 2010 Jan;78(1):145-53
references: 19858306
references: Curr Opin Mol Ther. 2007 Feb;9(1):12-24
references: 17330398
references: N Engl J Med. 2012 Dec 13;367(24):2284-95
references: 23136909
references: PLoS One. 2011 Apr 11;6(4):e18559
references: 21494604
references: PLoS Pathog. 2011 May;7(5):e1002032
references: 21573138
references: Eur J Immunol. 2011 Mar;41(3):682-93
references: 21264852
references: Int J Parasitol. 2011 Jan;41(1):3-20
references: 20816843
references: Nat Med. 2013 Feb;19(2):150-5
references: 23389615
references: Int J Parasitol. 2012 May 15;42(6):557-66
references: 22543040
references: N Engl J Med. 2008 Dec 11;359(24):2533-44
references: 19064623
references: Int Immunol. 1992 Jul;4(7):711-8
references: 1498082
references: Clin Exp Immunol. 1988 Mar;71(3):377-82
references: 3133141
references: Curr Opin Infect Dis. 1998 Oct;11(5):519-30
references: 17033417
references: Malar J. 2012 Jan 09;11:11
references: 22230255
references: Nat Med. 2011 Dec 18;18(1):120-7
references: 22179318
references: Lancet. 2002 Aug 24;360(9333):610-7
references: 12241933
references: J Immunol. 2009 Aug 1;183(3):2176-82
references: 19592645
references: N Engl J Med. 2011 Sep 15;365(11):1004-13
references: 21916638
references: Malar J. 2010 May 24;9:136
references: 20497536
references: Vaccine. 2011 Aug 11;29(35):6059-67
references: 21443960
references: N Engl J Med. 2009 Jul 30;361(5):468-77
references: 19641203
references: Expert Rev Vaccines. 2011 May;10(5):589-99
references: 21604980
references: PLoS One. 2010 Nov 29;5(11):e14114
references: 21124765
references: PLoS One. 2011;6(10):e25868
references: 22003411
references: PLoS One. 2011;6(7):e20775
references: 21779319
references: Microbes Infect. 2007 Oct;9(12-13):1439-46
references: 17913540
references: PLoS One. 2009 Jul 31;4(7):e6465
references: 19649245
references: Vaccine. 2006 May 29;24(22):4709-15
references: 16621181
references: Curr Opin Infect Dis. 2011 Oct;24(5):435-41
references: 21885920
references: Parasitol Res. 2004 Apr;92(6):449-52
references: 14963770
references: Sci Transl Med. 2010 Jul 14;2(40):40ra49
references: 20630856
references: Adv Parasitol. 2008;66:1-46
references: 18486688
references: Nat Immunol. 2009 Jan;10(1):116-125
references: 19029902
references: Trends Parasitol. 2010 Jul;26(7):363-9
references: 20466591
references: Science. 2011 Oct 28;334(6055):475-80
references: 21903775
references: Parasite Immunol. 2009 Sep;31(9):492-500
references: 19691554
references: N Engl J Med. 1997 Jan 9;336(2):86-91
references: 8988885
references: PLoS One. 2011 Jan 06;6(1):e14502
references: 21253594
references: Nat Med. 1999 Mar;5(3):340-3
references: 10086393
references: PLoS Pathog. 2010 Apr 29;6(4):e1000771
references: 20442856
references: Infect Immun. 2007 May;75(5):2283-90
references: 17307942
references: Lancet. 2011 May 21;377(9779):1770-6
references: 21514658
references: Mol Biochem Parasitol. 1996 Oct 30;81(2):151-70
references: 8898331
references: Am J Trop Med Hyg. 1991 Sep;45(3):297-308
references: 1928564
references: J Infect Dis. 2009 Aug 1;200(3):337-46
references: 19569965
references: J Exp Biol. 2003 Nov;206(Pt 21):3803-8
references: 14506215
references: Curr Genet. 2009 Apr;55(2):103-10
references: 19242694
references: PLoS Pathog. 2009 Apr;5(4):e1000369
references: 19343215
references: J Infect Dis. 2009 Aug 1;200(3):329-36
references: 19569964
references: J Immunol. 2008 Feb 1;180(3):1451-61
references: 18209040
references: PLoS Pathog. 2011 Mar;7(3):e1001318
references: 21445239
references: N Engl J Med. 2011 Nov 17;365(20):1863-75
references: 22007715
references: Curr Opin HIV AIDS. 2012 Jan;7(1):32-7
references: 22134340
references: Hum Vaccin. 2010 Jan;6(1):97-106
references: 19946222
references: Curr Opin Infect Dis. 2011 Dec;24(6):570-7
references: 22001944
references: Parasitology. 2005 Jan;130(Pt 1):13-22
references: 15700753
references: Nature. 2011 Nov 09;480(7378):534-7
references: 22080952
references: Eur J Immunol. 2008 Apr;38(4):1082-95
references: 18383042
references: Clin Microbiol Rev. 2009 Jan;22(1):13-36, Table of Contents
references: 19136431
references: Parasite Immunol. 2009 Sep;31(9):560-73
references: 19691559
references: PLoS Med. 2011 Jan 25;8(1):e1000398
references: 21311586
references: J Immunol. 2011 Aug 1;187(3):1347-57
references: 21715686
references: EMBO J. 1998 Jul 15;17(14):3816-26
references: 9669999
references: J Parasitol. 1993 Oct;79(5):763-7
references: 8410550
references: Expert Rev Vaccines. 2006 Oct;5(5):611-5
references: 17181435
references: Trends Parasitol. 2005 Feb;21(2):75-80
references: 15664530
references: N Engl J Med. 2008 Dec 11;359(24):2521-32
references: 19064627
references: Future Microbiol. 2011 Jun;6(6):693-704
references: 21707315
references: Am J Trop Med Hyg. 2001 Jan-Feb;64(1-2):9-11
references: 11425169
references: PLoS One. 2011;6(10):e25786
references: 21998698
references: Int J Biochem Cell Biol. 2009 Jul;41(7):1463-6
references: 19150410
references: Nat Rev Immunol. 2004 Mar;4(3):169-80
references: 15039754
references: J Immunol. 2010 Jul 1;185(1):263-72
references: 20519649
references: Trends Immunol. 2010 Feb;31(2):63-70
references: 20056484
references: J Immunol. 2005 Jan 1;174(1):449-55
references: 15611270
references: Immunol Rev. 2006 Oct;213:101-18
references: 16972899
references: Malar J. 2007 Dec 04;6:161
references: 18053225
references: Clin Microbiol Rev. 2011 Apr;24(2):377-410
references: 21482730
references: Science. 2012 Jul 13;337(6091):188
references: 22798607
references: Int J Parasitol. 2009 Jan;39(1):91-6
references: 18952091
references: Trends Parasitol. 2012 Jan;28(1):23-30
references: 22178537
references: PLoS Med. 2010 Jan 19;7(1):e1000218
references: 20098724
references: Science. 2010 May 14;328(5980):866-71
references: 20466925
references: Nat Immunol. 2008 Jul;9(7):725-32
references: 18563083
references: PLoS One. 2011 Feb 09;6(2):e16629
references: 21347415
references: Proc Natl Acad Sci U S A. 1990 Jul;87(14):5484-8
references: 2115172
references: Parasite Immunol. 2006 Jan-Feb;28(1-2):35-49
references: 16438675
references: Clin Infect Dis. 2008 Jan 15;46(2):165-71
references: 18171245
references: Lancet. 2012 Feb 4;379(9814):413-31
references: 22305225
references: Adv Immunol. 1989;45:283-334
references: 2665440
references: J Immunol. 2011 Oct 1;187(7):3738-50
references: 21876036
references: Nature. 1961 Nov 25;192:733-7
references: 13880318
references: Hum Vaccin. 2010 Jan;6(1):84-9
references: 19823032
references: Vaccine. 2010 Jul 12;28(31):4880-94
references: 20553771
references: Hum Vaccin. 2010 Jan;6(1):107-13
references: 19838068
references: Trends Parasitol. 2011 Feb;27(2):91-8
references: 20843745
references: J Infect Dis. 2009 Nov 15;200(10):1509-17
references: 19848588
references: J Mol Biol. 2001 Apr 13;307(5):1381-94
references: 11292349
references: J Infect Dis. 2002 Mar 15;185(6):820-7
references: 11920300
references: J Infect Dis. 2009 Dec 1;200(11):1646-9
references: 19877844
references: Curr Opin Infect Dis. 2007 Oct;20(5):476-81
references: 17762780
references: J Immunol. 2009 Jul 15;183(2):1013-21
references: 19561108
references: Lancet. 2005 Dec 10;366(9502):2012-8
references: 16338450
references: Lancet. 2004 Oct 16-22;364(9443):1411-20
references: 15488216
references: Hum Vaccin. 2011 Jan-Feb;7 Suppl:16-21
references: 21266857
references: Lancet. 2001 Dec 8;358(9297):1927-34
references: 11747915
references: Cell Microbiol. 2012 Mar;14(3):316-24
references: 22151703
references: Cell Host Microbe. 2011 Jun 16;9(6):451-62
references: 21669394
references: Nat Commun. 2011 Dec 20;2:601
references: 22186897
references: Curr Opin Immunol. 2007 Aug;19(4):424-9
references: 17624749
references: PLoS Med. 2005 Aug;2(8):e204
references: 16104831
references: J Infect Dis. 1998 Oct;178(4):1139-44
references: 9806046
references: J Immunol Methods. 2009 Jan 1;340(1):33-41
references: 18952093
references: Expert Rev Vaccines. 2011 Apr;10(4):471-86
references: 21506645
references: J Immunol. 2012 May 15;188(10):5054-62
references: 22504653
references: J Infect Dis. 2007 Jul 1;196(1):145-54
references: 17538895
references: PLoS One. 2011 Apr 27;6(4):e18891
references: 21556142
references: Trends Parasitol. 2011 Apr;27(4):168-75
references: 21377424
references: PLoS One. 2012;7(2):e31247
references: 22355349
references: Am J Trop Med Hyg. 1997 Oct;57(4):426-9
references: 9347958
references: Nat Med. 2000 Jan;6(1):91-5
references: 10613831
references: Nat Med. 2007 Sep;13(9):1035-41
references: 17704784
references: PLoS Pathog. 2011 Dec;7(12):e1002389
references: 22144890