title: Malaria Vaccine Development: Are Bacterial Flagellin Fusion Proteins the Bridge between Mouse and Humans?
abstract: In the past 25 years, the development of an effective malaria vaccine has become one of the biggest riddles in the biomedical sciences. Experimental data using animal infection models demonstrated that it is possible to induce protective immunity against different stages of malaria parasites. Nonetheless, the vast body of knowledge has generated disappointments when submitted to clinical conditions and presently a single antigen formulation has progressed to the point where it may be translated into a human vaccine. In parallel, new means to increase the protective effects of antigens in general have been pursued and depicted, such as the use of bacterial flagellins as carriers/adjuvants. Flagellins activate pathways in the innate immune system of both mice and humans. The recent report of the first Phase I clinical trial of a vaccine containing a Salmonella flagellin as carrier/adjuvant may fuel the use of these proteins in vaccine formulations. Herein, we review the studies on the use of recombinant flagellins as vaccine adjuvants with malarial antigens in the light of the current state of the art of malaria vaccine development. The available information indicates that bacterial flagellins should be seriously considered for malaria vaccine formulations to the development of effective human vaccines.
authors: Centro de Terapia Celular e Molecular (CTCMol), Universidade Federal de São Paulo, Escola Paulista de Medicina, Rua Mirassol 207, São Paulo 04044-010, SP, Brazil.
authors: Daniel Y
authors: DY
authors: Bargieri
authors: Irene S
authors: IS
authors: Soares
authors: Fabio T M
authors: FT
authors: Costa
authors: Catarina J
authors: CJ
authors: Braga
authors: Luis C S
authors: LC
authors: Ferreira
authors: Mauricio M
authors: MM
authors: Rodrigues
references: Vaccine. 2008 Nov 11;26(48):6132-42
references: 18804504
references: Eur J Immunol. 2009 Feb;39(2):359-71
references: 19152336
references: J Immunol. 2003 May 15;170(10):5165-75
references: 12734364
references: Vaccine. 2010 Mar 19;28(14):2580-92
references: 20097151
references: Nat Immunol. 2008 Oct;9(10):1171-8
references: 18724372
references: Am J Pathol. 2010 Jan;176(1):205-17
references: 20019192
references: Infect Immun. 2010 Jan;78(1):145-53
references: 19858306
references: Infect Immun. 1998 Apr;66(4):1500-6
references: 9529073
references: Mol Biochem Parasitol. 2007 May;153(1):31-40
references: 17343930
references: Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):13004-9
references: 19625622
references: N Engl J Med. 2008 Dec 11;359(24):2533-44
references: 19064623
references: Curr Mol Med. 2006 Mar;6(2):231-45
references: 16515513
references: Nature. 1967 Oct 14;216(5111):160-2
references: 6057225
references: PLoS One. 2008 May 21;3(5):e2257
references: 18493310
references: J Immunol. 2003 Apr 15;170(8):4102-10
references: 12682240
references: Vaccine. 2008 Jan 10;26(2):201-14
references: 18063235
references: PLoS One. 2009;4(3):e4708
references: 19262754
references: Mem Inst Oswaldo Cruz. 2007 Jun;102(3):335-9
references: 17568939
references: Infect Immun. 2005 Oct;73(10):6763-70
references: 16177354
references: Infect Immun. 2006 Jul;74(7):4330-8
references: 16790807
references: Vaccine. 2010 Dec 6;28(52):8268-74
references: 20969925
references: Int J Parasitol. 2007 Mar;37(3-4):273-83
references: 17224156
references: Infect Immun. 2006 Oct;74(10):5933-42
references: 16988273
references: Trends Parasitol. 2008 Feb;24(2):74-84
references: 18226584
references: Vaccine. 2010 Apr 1;28(16):2818-26
references: 20170765
references: J Immunol. 2010 Nov 15;185(10):5677-82
references: 21048152
references: Nat Med. 1998 Apr;4(4):397-402
references: 9546783
references: Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):14017-22
references: 18780790
references: J Clin Invest. 2010 Oct;120(10):3688-701
references: 20811151
references: Eur J Immunol. 2010 Dec;40(12):3528-34
references: 21072873
references: Trends Parasitol. 2008 Jan;24(1):29-34
references: 18023618
references: Science. 1989 Apr 7;244(4900):70-2
references: 2468182
references: Infect Immun. 2006 Jan;74(1):313-20
references: 16368986
references: Vaccine. 2010 Feb 3;28(5):1373-82
references: 19932669
references: Cell Mol Life Sci. 2010 May;67(10):1643-51
references: 20229126
references: J Exp Med. 1990 Jan 1;171(1):299-306
references: 1688609
references: Nature. 2001 Apr 26;410(6832):1099-103
references: 11323673
references: Infect Immun. 2006 Dec;74(12):6929-39
references: 17030584
references: J Infect Dis. 2009 Aug 1;200(3):337-46
references: 19569965
references: Proc Natl Acad Sci U S A. 2005 Aug 23;102(34):12194-9
references: 16103357
references: Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):7963-7
references: 1680235
references: Immunol Lett. 2009 Aug 15;125(2):114-8
references: 19555720
references: Vaccine. 1992;10(6):405-11
references: 1376012
references: Curr Opin Infect Dis. 2007 Oct;20(5):467-75
references: 17762779
references: Expert Opin Biol Ther. 2007 Dec;7(12):1841-52
references: 18034650
references: J Immunol. 2008 May 15;180(10):6808-15
references: 18453601
references: Malar J. 2003 Nov 14;2(1):39
references: 14617378
references: J Immunol. 2009 Jun 15;182(12):7539-47
references: 19494277
references: Int J Parasitol. 2010 Aug 15;40(10):1155-61
references: 20451527
references: J Exp Med. 1992 Apr 1;175(4):895-905
references: 1372647
references: Science. 1989 Dec 22;246(4937):1603-6
references: 2480642
references: N Engl J Med. 2008 Dec 11;359(24):2521-32
references: 19064627
references: Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3300-4
references: 1707538
references: J Virol. 2008 Nov;82(22):10975-85
references: 18787007
references: Nat Immunol. 2003 Dec;4(12):1247-53
references: 14625549
references: Curr Mol Med. 2006 Mar;6(2):187-203
references: 16515510
references: Hum Vaccin. 2010 Jan;6(1):90-6
references: 19806009
references: Trends Microbiol. 2004 Nov;12(11):509-17
references: 15488392
references: J Leukoc Biol. 2007 Sep;82(3):509-18
references: 17586660
references: Mol Med. 1999 Jul;5(7):459-70
references: 10449807
references: Trends Parasitol. 2010 May;26(5):230-5
references: 20189879
references: J Immunol. 1994 Nov 15;153(10):4636-48
references: 7525709
references: Nat Immunol. 2008 Jul;9(7):725-32
references: 18563083
references: Int Immunol. 1991 Jun;3(6):579-85
references: 1716146
references: Nature. 1989 Sep 28;341(6240):323-6
references: 2477703
references: Nat Immunol. 2006 Jun;7(6):569-75
references: 16648853
references: Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11491-6
references: 11553779
references: Hum Vaccin. 2010 Jan;6(1):84-9
references: 19823032
references: Curr Opin Struct Biol. 2010 Oct;20(5):560-6
references: 20655195
references: Infect Immun. 2005 Sep;73(9):5936-44
references: 16113314
references: PLoS One. 2008 Jul 30;3(7):e2830
references: 18665258
references: Cell Host Microbe. 2009 Apr 23;5(4):386-96
references: 19380117
references: Cell Microbiol. 2010 Jul;12(7):930-8
references: 20088947
references: PLoS One. 2007 Aug 15;2(8):e707
references: 17710125
references: Vaccine. 2009 Mar 4;27(10):1651-60
references: 19038302
references: Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7648-53
references: 9636204
references: Nature. 2006 Dec 14;444(7121):937-40
references: 17151604
references: Infect Immun. 1996 Jul;64(7):2602-8
references: 8698485
references: Nat Med. 2008 Sep;14(9):954-8
references: 18758447
references: Proc Natl Acad Sci U S A. 2005 Mar 29;102(13):4836-41
references: 15781866
references: Nature. 2005 Jan 13;433(7022):164-7
references: 15580261
references: J Immunol. 2003 Nov 15;171(10):4984-9
references: 14607893
references: J Immunol. 2004 Jun 1;172(11):6922-30
references: 15153511
references: J Biol Chem. 2010 Oct 15;285(42):32087-95
references: 20702413
references: Nat Immunol. 2006 Mar;7(3):318-25
references: 16444259
references: Infect Immun. 1993 Jun;61(6):2462-7
references: 8363656
references: PLoS One. 2009 Nov 05;4(11):e7717
references: 19890387
references: Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5214-8
references: 7685119
references: J Mol Biol. 2010 Apr 2;397(3):826-34
references: 20109466
references: Adv Immunol. 1995;60:105-49
references: 8607369
references: Res Microbiol. 1997 Mar-Apr;148(3):217-28
references: 9765802
references: Nat Med. 2000 Jan;6(1):91-5
references: 10613831