Antigens for pre-erythrocytic malaria vaccines: building on success.
Immunization with attenuated pre-erythrocytic malaria parasites can confer sterile protection against malaria in humans and rodents, and a single pre-erythrocytic antigen incorporated in a subunit vaccine has substantially reduced clinical Plasmodium falciparum malaria episodes in African infants during phase 2 trials. Building upon this success has been hindered by technical obstacles that limit research on pre-erythrocytic parasites, especially the liver stage (LS) parasites, and by an incomplete understanding of the immune mechanisms that confer protection in humans. Recent improvements in growing and isolating LS parasites have allowed progress in defining the transcriptome and proteome of the LS parasite, although more work remains to be done particularly for the early LS parasite of P. falciparum. Next generation pre-erythrocytic antigens can be assessed and prioritized based on immunization studies in animals, and on models of immunity such as attenuated parasite vaccines that confer sterile protection or naturally acquired LS-specific immune responses that correlate with protection in endemic areas. Although mechanisms of protection in humans remain poorly understood, the availability of a human malaria challenge model for early clinical testing of candidate vaccines is a valuable tool to confirm which immunogens should move forward to larger field trials.
Speake
C
C
Malaria Program, Seattle Biomedical Research Institute, Seattle, WA 98109, USA.
Duffy
P E
PE
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D010963:Plasmodium falciparum / Q000276:immunology*; D012377:Rodentia
D000953:Antigens, Protozoan; D017780:Malaria Vaccines
Nature. 2008 Oct 9;455(7214):757-63
18843361
Immunology. 1994 May;82(1):164-8
7913914
Infect Immun. 1999 Jul;67(7):3424-9
10377122
N Engl J Med. 2008 Dec 11;359(24):2533-44
19064623
PLoS One. 2008;3(10):e3549
18958160
Infect Immun. 2004 Mar;72(3):1594-602
14977966
J Immunol. 1992 Sep 15;149(6):2103-9
1517574
Cell. 2007 Nov 2;131(3):492-504
17981117
Nat Med. 2003 Jun;9(6):729-35
12766765
J Exp Med. 1990 Nov 1;172(5):1353-7
2146361
PLoS One. 2007 Dec 26;2(12):e1371
18159254
Nature. 1967 Oct 14;216(5111):160-2
6057225
Parasite Immunol. 2002 Apr;24(4):221-3
12010486
Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9952-7
12886016
J Exp Med. 2003 Apr 21;197(8):1045-50
12707302
Nat Med. 2004 Apr;10(4):406-10
15034567
Am J Trop Med Hyg. 1991 Nov;45(5):539-47
1951863
Nat Med. 2002 Feb;8(2):166-70
11821901
Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):14017-22
18780790
Science. 2005 Jan 7;307(5706):82-6
15637271
Am J Trop Med Hyg. 2006 May;74(5):708-15
16687667
Am J Med Sci. 1973 Sep;266(3):169-77
4583408
PLoS One. 2008 Apr 30;3(4):e2027
18446217
Infect Immun. 2005 Jul;73(7):4363-9
15972531
Immunology. 1993 Sep;80(1):1-5
7902331
J Infect Dis. 2007 Aug 15;196(4):608-16
17624848
J Exp Biol. 2003 Nov;206(Pt 21):3803-8
14506215
PLoS One. 2009;4(2):e4480
19214236
Curr Mol Med. 2006 Mar;6(2):169-85
16515509
Mol Biochem Parasitol. 2004 Sep;137(1):161-8
15279962
Int J Parasitol. 2006 Oct;36(12):1283-93
16890231
Nature. 2002 Oct 3;419(6906):498-511
12368864
Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):3022-7
15699336
Lancet. 2007 Nov 3;370(9598):1543-51
17949807
J Infect Dis. 2009 Mar 15;199(6):899-903
19434915
J Immunol. 2008 Dec 15;181(12):8552-8
19050274
N Engl J Med. 2008 Dec 11;359(24):2521-32
19064627
Science. 1986 May 16;232(4752):881-4
3085218
Int Immunol. 1991 Jun;3(6):579-85
1716146
Nature. 1989 Sep 28;341(6240):323-6
2477703
J Infect Dis. 1999 Apr;179(4):980-8
10068595
J Immunol. 2004 Feb 15;172(4):2487-95
14764721
J Infect Dis. 2008 Feb 15;197(4):519-26
18275273
J Immunol. 1995 Oct 15;155(8):4072-7
7561118
J Infect Dis. 1999 Nov;180(5):1656-64
10515829
Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):305-10
18172196
Mol Biochem Parasitol. 2005 Aug;142(2):177-83
15876462
PLoS Clin Trials. 2006 Oct 20;1(6):e29
17053830
PLoS Pathog. 2008 Aug 08;4(8):e1000121
18688281
J Immunol. 2007 Sep 15;179(6):4193-201
17785859
Curr Opin Infect Dis. 2007 Oct;20(5):461-6
17762778
Trends Parasitol. 2001 May;17(5):219-23
11323304
PLoS Med. 2004 Nov;1(2):e33
15526058
Nature. 2008 Oct 9;455(7214):751-6
18843360
Immunol Cell Biol. 2009 Jul;87(5):377-90
19417768
Nature. 2006 Dec 14;444(7121):937-40
17151604
Lancet. 2005 Dec 10;366(9502):2012-8
16338450
Cell Microbiol. 2007 May;9(5):1215-22
17223931
Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):4066-8
7732032
Nature. 2008 Oct 9;455(7214):799-803
18843368
Nature. 2005 Jan 13;433(7022):164-7
15580261
J Immunol. 1977 Apr;118(4):1322-7
321689
J Immunol. 1991 Feb 1;146(3):1020-5
1988490
Nature. 2002 Oct 3;419(6906):512-9
12368865