title: Malaria invasion ligand RH5 and its prime candidacy in blood-stage malaria vaccine design.
abstract: With drug resistance to available therapeutics continuing to develop against Plasmodium falciparum malaria, the development of an effective vaccine candidate remains a major research goal. Successful interruption of invasion of parasites into erythrocytes during the blood stage of infection will prevent the severe clinical symptoms and complications associated with malaria. Previously studied blood stage antigens have highlighted the hurdles that are inherent to this life-cycle stage, namely that highly immunogenic antigens are also globally diverse, resulting in protection only against the vaccine strain, or that naturally acquired immunity to blood stage antigens do not always correlate with actual protection. The blood stage antigen reticulocyte binding homolog RH5 is essential for parasite viability, has globally limited diversity, and is associated with protection from disease. Here we summarize available information on this invasion ligand and recent findings that highlight its candidacy for inclusion in a blood-stage malaria vaccine.
authors.affiliation: a Blood-Borne Parasites; Lindsley Kimball Research Institute; New York Blood Center ; New York , NY , USA.
authors.forename: Rosalynn L
authors.initials: RL
authors.lastname: Ord
authors.forename: Marilis
authors.initials: M
authors.lastname: Rodriguez
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Lobo
mesh_terms: D002352:Carrier Proteins / Q000276:immunology*; D055808:Drug Discovery / Q000639:trends*; D006801:Humans; D008288:Malaria / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000276:immunology* / Q000302:isolation & purification*
chemical_list: D002352:Carrier Proteins; D017780:Malaria Vaccines; C531020:RH5 protein, Plasmodium falciparum
keywords: Plasmodium falciparum; RH5; invasion; malaria vaccine; vaccine development
references.citation: Malar J. 2006;5:100
references.pmid: 17087826
references.citation: Blood. 2011 Aug 18;118(7):1923-33
references.pmid: 21685372
references.citation: Mol Biochem Parasitol. 2007 Jan;151(1):100-10
references.pmid: 17125854
references.citation: Nature. 2011 Dec 22;480(7378):534-7
references.pmid: 22080952
references.citation: N Engl J Med. 2009 Jul 30;361(5):455-67
references.pmid: 19641202
references.citation: Cell. 1992 Jun 26;69(7):1213-26
references.pmid: 1617731
references.citation: Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9648-53
references.pmid: 10920203
references.citation: N Engl J Med. 2012 Dec 13;367(24):2284-95
references.pmid: 23136909
references.citation: Cell Host Microbe. 2008 Jul 17;4(1):40-51
references.pmid: 18621009
references.citation: Front Microbiol. 2014 Jun 30;5:314
references.pmid: 25071730
references.citation: Mol Biochem Parasitol. 2013 Feb;187(2):103-10
references.pmid: 23305874
references.citation: Science. 2005 Aug 26;309(5739):1384-7
references.pmid: 16123303
references.citation: Nature. 1980 Mar 27;284(5754):366-8
references.pmid: 7360274
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5348-52
references.pmid: 19279206
references.citation: Clin Exp Immunol. 1982 Aug;49(2):297-309
references.pmid: 6751636
references.citation: Infect Immun. 2008 May;76(5):2240-8
references.pmid: 18316390
references.citation: Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):20735-40
references.pmid: 24297912
references.citation: Hum Vaccin Immunother. 2012 Jun;8(6):706-14
references.pmid: 22508415
references.citation: Infect Immun. 2003 Dec;71(12):6742-6
references.pmid: 14638759
references.citation: PLoS Pathog. 2005 Dec;1(4):e44
references.pmid: 16389297
references.citation: Expert Rev Vaccines. 2013 Feb;12(2):129-41
references.pmid: 23414405
references.citation: Cell Microbiol. 2013 Aug;15(8):1304-12
references.pmid: 23617720
references.citation: Nature. 2014 Nov 20;515(7527):427-30
references.pmid: 25132548
references.citation: PLoS One. 2011;6(2):e17102
references.pmid: 21386888
references.citation: Science. 1985 Nov 1;230(4725):553-6
references.pmid: 3901257
references.citation: Mol Biochem Parasitol. 2001 Aug;116(1):55-63
references.pmid: 11463466
references.citation: N Engl J Med. 2011 Nov 17;365(20):1863-75
references.pmid: 22007715
references.citation: PLoS Pathog. 2011 Sep;7(9):e1002199
references.pmid: 21909261
references.citation: Hum Vaccin Immunother. 2012 Jun;8(6):823-7
references.pmid: 22699438
references.citation: Int J Parasitol. 2009 Jan;39(1):91-6
references.pmid: 18952091
references.citation: PLoS Pathog. 2012;8(11):e1002991
references.pmid: 23144611
references.citation: Mol Biochem Parasitol. 2006 Aug;148(2):144-60
references.pmid: 16644028
references.citation: Science. 1975 Feb 28;187(4178):748-50
references.pmid: 803712
references.citation: Infect Immun. 2002 Oct;70(10):5779-89
references.pmid: 12228308
references.citation: Nat Commun. 2011;2:601
references.pmid: 22186897
references.citation: Dev Biol. 1998 Feb 15;194(2):152-65
references.pmid: 9501026
references.citation: Mol Microbiol. 2010 Feb;75(4):990-1006
references.pmid: 20487292
references.citation: Biochem Biophys Res Commun. 2011 Jun 3;409(2):253-9
references.pmid: 21569761
references.citation: Mol Biochem Parasitol. 2000 Jan 5;105(1):105-13
references.pmid: 10613703
references.citation: Vaccine. 2013 Jan 2;31(2):373-9
references.pmid: 23146673
references.citation: Mol Microbiol. 2009 May;72(3):578-89
references.pmid: 19400777
references.citation: Nature. 2012 Jul 19;487(7407):375-9
references.pmid: 22722859
references.citation: J Mol Biol. 2008 Jun 27;380(1):252-63
references.pmid: 18508079
references.citation: Nature. 2008 Jan 10;451(7175):207-10
references.pmid: 18185591
references.citation: Blood. 1986 May;67(5):1519-21
references.pmid: 3516259
references.citation: PLoS One. 2012;7(1):e30251
references.pmid: 22253925
references.citation: Proc Natl Acad Sci U S A. 2011 May 3;108(18):7553-8
references.pmid: 21502513
references.citation: Mol Biochem Parasitol. 1994 Mar;64(1):55-63
references.pmid: 8078523
references.citation: Lancet. 2012 Feb 4;379(9814):413-31
references.pmid: 22305225
references.citation: Vaccine. 2004 Dec 16;23(5):718-28
references.pmid: 15542195
references.citation: Mol Microbiol. 2013 Apr;88(1):20-34
references.pmid: 23347042
references.citation: Nature. 1981 Nov 26;294(5839):361-4
references.pmid: 7312033
references.citation: Nat Biotechnol. 2003 Jan;21(1):71-6
references.pmid: 12483221
references.citation: PLoS One. 2009;4(3):e4708
references.pmid: 19262754
references.citation: N Engl J Med. 2011 Sep 15;365(11):1004-13
references.pmid: 21916638
references.citation: Infect Immun. 2009 Apr;77(4):1689-99
references.pmid: 19204093
references.citation: Proc Natl Acad Sci U S A. 2015 Jan 27;112(4):1179-84
references.pmid: 25583518
references.citation: Science. 1994 Jun 24;264(5167):1941-4
references.pmid: 8009226
references.citation: Cell Host Microbe. 2015 Jan 14;17(1):130-9
references.pmid: 25590760
references.citation: Cell Host Microbe. 2011 Jan 20;9(1):9-20
references.pmid: 21238943
references.citation: Malar J. 2012;11:361
references.pmid: 23110555
references.citation: Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2518-23
references.pmid: 14983041
references.citation: Mol Biochem Parasitol. 2002 May;121(2):275-8
references.pmid: 12034462
references.citation: J Mol Biol. 2011 Jun 3;409(2):225-37
references.pmid: 21501621
references.citation: Dev Dyn. 1993 Apr;196(4):252-62
references.pmid: 8219348
references.citation: Mol Biochem Parasitol. 1988 Jan 1;27(1):23-34
references.pmid: 2830508
references.citation: Vaccine. 2013 Sep 23;31(41):4647-54
references.pmid: 23933337
references.citation: J Clin Invest. 1990 Aug;86(2):618-24
references.pmid: 2200806
references.citation: Hum Vaccin Immunother. 2012 Mar;8(3):411-4
references.pmid: 22330956
references.citation: J Infect Dis. 2013 Nov 15;208(10):1679-87
references.pmid: 23904294
references.citation: Infect Immun. 2001 Jun;69(6):3635-45
references.pmid: 11349024
references.citation: Infect Immun. 2001 Feb;69(2):1084-92
references.pmid: 11160005
references.citation: PLoS One. 2008;3(10):e3300
references.pmid: 18827878
references.citation: Vaccine. 2010 Jun 17;28(27):4384-93
references.pmid: 20434554
references.citation: Elife. 2014;3. doi: 10.7554/eLife.04187
references.pmid: 25296023
references.citation: Blood. 2003 Jun 1;101(11):4628-31
references.pmid: 12576308
references.citation: Mol Microbiol. 2007 Jul;65(2):231-49
references.pmid: 17630968
references.citation: Lancet Infect Dis. 2013 Apr;13(4):319-27
references.pmid: 23454164
references.citation: Genome Res. 2004 Oct;14(10B):2076-82
references.pmid: 15489329
references.citation: Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17327-32
references.pmid: 20855594
references.citation: J Biol Chem. 2003 Apr 18;278(16):14480-6
references.pmid: 12556470
references.citation: Arch Biochem Biophys. 1997 Nov 1;347(1):85-92
references.pmid: 9344468
references.citation: Nat Med. 2003 Jan;9(1):87-92
references.pmid: 12469115
references.citation: Hum Vaccin Immunother. 2013 Sep;9(9):1831-40
references.pmid: 23778312
references.citation: Mol Biochem Parasitol. 2001 Sep 28;117(1):1-10
references.pmid: 11551627
references.citation: Int J Parasitol. 2009 Feb;39(3):371-80
references.pmid: 19000690
references.citation: Infect Immun. 2006 Aug;74(8):4573-80
references.pmid: 16861644
references.citation: J Exp Med. 2001 Dec 3;194(11):1571-81
references.pmid: 11733572
references.citation: Infect Immun. 2005 Jan;73(1):422-30
references.pmid: 15618180
references.citation: Malar J. 2012;11:11
references.pmid: 22230255
references.citation: Parasite Immunol. 2014 Mar;36(3):131-9
references.pmid: 24188045
references.citation: J Gen Virol. 1996 Feb;77 ( Pt 2 ):183-8
references.pmid: 8627221
references.citation: Trends Parasitol. 2001 Jun;17(6):297-9
references.pmid: 11378038
references.citation: Clin Vaccine Immunol. 2012 Feb;19(2):261-7
references.pmid: 22155768
references.citation: Int J Parasitol. 2004 Dec;34(13-14):1413-29
references.pmid: 15582519
references.citation: Infect Immun. 2004 Oct;72(10):6185-9
references.pmid: 15385530
references.citation: Infect Immun. 2014 Jan;82(1):152-64
references.pmid: 24126527
references.citation: PLoS Pathog. 2010 Feb;6(2):e1000746
references.pmid: 20140184
references.citation: J Infect Dis. 2013 Jul;208(1):149-58
references.pmid: 23539744
references.citation: Mol Biochem Parasitol. 2006 Feb;145(2):205-15
references.pmid: 16289357
references.citation: Infect Immun. 2009 Mar;77(3):1165-74
references.pmid: 19139189
references.citation: PLoS Pathog. 2010;6(6):e1000968
references.pmid: 20585558
references.citation: J Infect Dis. 2014 Mar 1;209(5):789-98
references.pmid: 24133188
references.citation: PLoS One. 2009;4(4):e5254
references.pmid: 19390585
references.citation: Malar J. 2008;7:197
references.pmid: 18828893
references.citation: J Cell Biol. 1978 Apr;77(1):72-82
references.pmid: 96121
references.citation: Mol Microbiol. 2005 Jan;55(1):162-74
references.pmid: 15612925
references.citation: EMBO J. 2003 Mar 3;22(5):1047-57
references.pmid: 12606570
references.citation: Malar J. 2014;13:326
references.pmid: 25135070
references.citation: J Immunol. 2014 Jan 1;192(1):245-58
references.pmid: 24293631