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An Immunomics Approach to Schistosome Antigen Discovery: Antibody Signatures of Naturally Resistant and Chronically Infected Individuals from Endemic Areas
Schistosomiasis is a neglected tropical disease that kills as many as 300,000 people each year. Mass drug administration is widely used to control schistosomiasis, but fails to prevent rapid reinfection in endemic areas. There is a desperate need for a prophylactic vaccine; however, very few candidates have been developed. Herein, we take advantage of recent advances in systems biology and longitudinal studies in schistosomiasis endemic areas to pilot an immunomics approach to the discovery of vaccine antigens. The emerging field of immunomics enables the determination of an “antibody signature” to a pathogen proteome for both resistant and susceptible individuals. We constructed the first protein microarray for a multi-cellular pathogen and probed it with sera from naturally resistant vs. susceptible individuals from a high transmission area in Northeastern Brazil. Using multi-dimensional cluster analysis, we showed that resistant individuals mounted a distinct and robust IgG1 antibody signature to a small set of newly discovered and well-characterized surface antigens in contrast to infected individuals. This antigen discovery strategy can lead to identification of several potentially protective and safe schistosomiasis vaccine antigens.
Vyšlo v časopise: An Immunomics Approach to Schistosome Antigen Discovery: Antibody Signatures of Naturally Resistant and Chronically Infected Individuals from Endemic Areas. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1004033
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004033Souhrn
Schistosomiasis is a neglected tropical disease that kills as many as 300,000 people each year. Mass drug administration is widely used to control schistosomiasis, but fails to prevent rapid reinfection in endemic areas. There is a desperate need for a prophylactic vaccine; however, very few candidates have been developed. Herein, we take advantage of recent advances in systems biology and longitudinal studies in schistosomiasis endemic areas to pilot an immunomics approach to the discovery of vaccine antigens. The emerging field of immunomics enables the determination of an “antibody signature” to a pathogen proteome for both resistant and susceptible individuals. We constructed the first protein microarray for a multi-cellular pathogen and probed it with sera from naturally resistant vs. susceptible individuals from a high transmission area in Northeastern Brazil. Using multi-dimensional cluster analysis, we showed that resistant individuals mounted a distinct and robust IgG1 antibody signature to a small set of newly discovered and well-characterized surface antigens in contrast to infected individuals. This antigen discovery strategy can lead to identification of several potentially protective and safe schistosomiasis vaccine antigens.
Zdroje
1. van der WerfMJ, de VlasSJ, BrookerS, LoomanCWN, NagelkerkeNJD, et al. (2003) Quantification of clinical morbidity associated with schistosome infection in sub-Saharan Africa. Acta Trop 86 : 125–139.
2. KingCH, DickmanK, TischDJ (2005) Reassessment of the cost of chronic helmintic infection: a meta-analysis of disability-related outcomes in endemic schistosomiasis. Lancet 365 : 1561–1569.
3. KingCH, Dangerfield-ChaM (2008) The unacknowledged impact of chronic schistosomiasis. Chronic Illn 4 : 65–79.
4. SteinmannP, KeiserJ, BosR, TannerM, UtzingerJ (2006) Schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people at risk. Lancet Infect Dis 6 : 411–425.
5. GrayDJ, McManusDP, LiY, WilliamsGM, BergquistR, et al. (2010) Schistosomiasis elimination: lessons from the past guide the future. Lancet Infect Dis 10 : 733–736.
6. FallonPG, DoenhoffMJ (1994) Drug-resistant schistosomiasis: resistance to praziquantel and oxamniquine induced in Schistosoma mansoni in mice is drug specific. Am J Trop Med Hyg 51 : 83–88.
7. WangW, WangL, LiangY-S (2012) Susceptibility or resistance of praziquantel in human schistosomiasis: a review. Parasitol Res 111 : 1871–1877.
8. FenwickA (2006) Waterborne infectious diseases—could they be consigned to history? Science 313 : 1077–1081.
9. ClementsACA, Bosqué-OlivaE, SackoM, LandouréA, DembéléR, et al. (2009) A comparative study of the spatial distribution of schistosomiasis in Mali in 1984–1989 and 2004–2006. PLoS Negl Trop Dis 3: e431.
10. WoolhouseME (1998) Patterns in parasite epidemiology: the peak shift. Parasitol Today 14 : 428–434.
11. BlackCL, MwinziPNM, MuokEMO, AbudhoB, FitzsimmonsCM, et al. (2010) Influence of exposure history on the immunology and development of resistance to human Schistosomiasis mansoni. PLoS Negl Trop Dis 4: e637.
12. SkellyPJ, Alan WilsonR (2006) Making sense of the schistosome surface. Adv Parasitol 63 : 185–284.
13. NuttallPA, TrimnellAR, KazimirovaM, LabudaM (2006) Exposed and concealed antigens as vaccine targets for controlling ticks and tick-borne diseases. Parasite Immunol 28 : 155–163.
14. KnoxDP (2000) Development of vaccines against gastrointestinal nematodes. Parasitology 120 Suppl: S43–S61
15. JohnsonKS, HarrisonGB, LightowlersMW, O'HoyKL, CougleWG, et al. (1989) Vaccination against ovine cysticercosis using a defined recombinant antigen. Nature 338 : 585–587.
16. LightowlersMW, LawrenceSB, GauciCG, YoungJ, RalstonMJ, et al. (1996) Vaccination against hydatidosis using a defined recombinant antigen. Parasite Immunol 18 : 457–462.
17. RiveauG, DeplanqueD, RemouéF, SchachtA-M, VodougnonH, et al. (2012) Safety and immunogenicity of rSh28GST antigen in humans: phase 1 randomized clinical study of a vaccine candidate against urinary schistosomiasis. PLoS Negl Trop Dis 6: e1704.
18. TendlerM, SimpsonAJG (2008) The biotechnology-value chain: development of Sm14 as a schistosomiasis vaccine. Acta Trop 108 : 263–266.
19. HotezPJ, BethonyJM, DiemertDJ, PearsonM, LoukasA (2010) Developing vaccines to combat hookworm infection and intestinal schistosomiasis. Nature Rev Microbiol 8 : 814–826.
20. McManusDP, LoukasA (2008) Current status of vaccines for schistosomiasis. Clin Microbiol Rev 21 : 225–242.
21. LoukasA, GazeS, MulvennaJP, GasserRB, BrindleyPJ, et al. (2011) Vaccinomics for the major blood feeding helminths of humans. OMICS 15 : 567–577.
22. MartinsVP, PinheiroCS, FigueiredoBCP, AssisNRG, MoraisSB, et al. (2012) Vaccination with enzymatically cleaved GPI-anchored proteins from Schistosoma mansoni induces protection against challenge infection. Clin Dev Immunol 2012 : 962538.
23. Castro-BorgesW, DowleA, CurwenRS, Thomas-OatesJ, WilsonRA (2011) Enzymatic shaving of the tegument surface of live schistosomes for proteomic analysis: a rational approach to select vaccine candidates. PLoS Negl Trop Dis 5: e993.
24. CardosoFC, MacedoGC, GavaE, KittenGT, MatiVL, et al. (2008) Schistosoma mansoni tegument protein Sm29 is able to induce a Th1-type of immune response and protection against parasite infection. PLoS Negl Trop Dis 2: e308.
25. AhmadG, ZhangW, TorbenW, AhrorovA, DamianRT, et al. (2011) Preclinical prophylactic efficacy testing of Sm-p80-based vaccine in a nonhuman primate model of Schistosoma mansoni infection and immunoglobulin G and E responses to Sm-p80 in human serum samples from an area where schistosomiasis is endemic. J Infect Dis 204 : 1437–1449.
26. TranMH, PearsonMS, BethonyJM, SmythDJ, JonesMK, et al. (2006) Tetraspanins on the surface of Schistosoma mansoni are protective antigens against schistosomiasis. Nature Med 12 : 835–840.
27. YoungND, JexAR, LiB, LiuS, YangL, et al. (2012) Whole-genome sequence of Schistosoma haematobium. Nature Genet 44 : 221–225.
28. Schistosoma japonicum Genome Sequencing and Functional Analysis Consortium (2009) The Schistosoma japonicum genome reveals features of host-parasite interplay. Nature 460 : 345–351.
29. BerrimanM, HaasBJ, LoVerdePT, WilsonRA, DillonGP, et al. (2009) The genome of the blood fluke Schistosoma mansoni. Nature 460 : 352–358.
30. BraschiS, WilsonRA (2006) Proteins exposed at the adult schistosome surface revealed by biotinylation. Mol Cell Proteomics 5 : 347–356.
31. MulvennaJ, MoertelL, JonesMK, NawaratnaS, LovasEM, et al. (2010) Exposed proteins of the Schistosoma japonicum tegument. Int J Parasitol 40 : 543–554.
32. GazzinelliA, BethonyJ, FragaLA, LoVerdePT, Correa-OliveiraR, et al. (2001) Exposure to Schistosoma mansoni infection in a rural area of Brazil. I: water contact. Trop Med Int Health 6 : 126–135.
33. BethonyJ, WilliamsJT, KloosH, BlangeroJ, Alves-FragaL, et al. (2001) Exposure to Schistosoma mansoni infection in a rural area in Brazil. II: household risk factors. Trop Med Int Health 6 : 136–145.
34. BethonyJ, WilliamsJT, BrookerS, GazzinelliA, GazzinelliMF, et al. (2004) Exposure to Schistosoma mansoni infection in a rural area in Brazil. Part III: household aggregation of water-contact behaviour. Trop Med Int Health 9 : 381–389.
35. VianaIR, SherA, CarvalhoOS, MassaraCL, Eloi-SantosSM, et al. (1994) Interferon-gamma production by peripheral blood mononuclear cells from residents of an area endemic for Schistosoma mansoni. Trans R Soc Trop Med Hyg 88 : 466–470.
36. CaldasIR, Correa-OliveiraR, ColosimoE, CarvalhoOS, MassaraCL, et al. (2000) Susceptibility and resistance to Schistosoma mansoni reinfection: parallel cellular and isotypic immunologic assessment. Am J Trop Med Hyg 62 : 57–64.
37. Bahia-OliveiraLM, SimpsonAJ, Alves-OliveiraLF, Carvalho-QueirozC, SilveiraAM, et al. (1996) Evidence that cellular immune responses to soluble and membrane associated antigens are independently regulated during human schistosomiasis mansoni. Parasite Immunol 18 : 53–63.
38. DriguezP, DoolanDL, LoukasA, FelgnerPL, McManusDP (2010) Schistosomiasis vaccine discovery using immunomics. Parasit Vectors 3 : 4.
39. DiemertDJ, PintoAG, FreireJ, JariwalaA, SantiagoH, et al. (2012) Generalized urticaria induced by the Na-ASP-2 hookworm vaccine: implications for the development of vaccines against helminths. J Allergy Clin Immunol 130 : 169–76.e6.
40. HartiganJA, WongMA (1979) Algorithm AS 136: a k-means clustering algorithm. J Royal Stat Soc Series C (Appl Stats) 28 : 100–108.
41. DefaysD (1977) An efficient algorithm for a complete link method. The Computer Journal 20 : 364–366.
42. De GrootAS (2009) Exploring the immunome: A brave new world for human vaccine development. Hum Vaccin 5 : 790–793.
43. VigilA, DaviesDH, FelgnerPL (2010) Defining the humoral immune response to infectious agents using high-density protein microarrays. Future Microbiol 5 : 241–251.
44. DaviesDH, MolinaDM, WrammertJ, MillerJ, HirstS, et al. (2007) Proteome-wide analysis of the serological response to vaccinia and smallpox. Proteomics 7 : 1678–1686.
45. HarropR, JenningsN, MountfordAP, CoulsonPS, WilsonRA (2000) Characterization, cloning and immunogenicity of antigens released by transforming cercariae of Schistosoma mansoni. Parasitology 121 : 385–394.
46. MoloneyNA, WebbeG (1990) Antibody is responsible for the passive transfer of immunity to mice from rabbits, rats or mice vaccinated with attenuated Schistosoma japonicum cercariae. Parasitology 100 : 235–239.
47. CioliD, BlumK, RuppelA (1978) Schistosoma mansoni: relationship between parasite age and time of spontaneous elimination from the rat. Exp Parasitol 45 : 74–80.
48. CêtreC, PierrotC, CocudeC, LafitteS, CapronA, et al. (1999) Profiles of Th1 and Th2 cytokines after primary and secondary infection by Schistosoma mansoni in the semipermissive rat host. Infect Immun 67 : 2713–2719.
49. BarkerRH, SrivastavaBS, SuriP, GoldbergM, KnopfPM (1985) Immunoprecipitation analysis of radiolabelled protein antigens biosynthesized in vitro by S. mansoni. I. Identification of antigens uniquely recognized by protective antibodies. J Immunol 134 : 1192–1201.
50. SepulvedaJ, TremblayJM, DeGnoreJP, SkellyPJ, ShoemakerCB (2010) Schistosoma mansoni host-exposed surface antigens characterized by sera and recombinant antibodies from schistosomiasis-resistant rats. Int J Parasitol 40 : 1407–1417.
51. DoenhoffMJ, SabahAA, FletcherC, WebbeG, BainJ (1987) Evidence for an immune-dependent action of praziquantel on Schistosoma mansoni in mice. Trans R Soc Trop Med Hyg 81 : 947–951.
52. BrindleyPJ, SherA (1987) The chemotherapeutic effect of praziquantel against Schistosoma mansoni is dependent on host antibody response. J Immunol 139 : 215–220.
53. WalterK, FulfordAJC, McBeathR, JosephS, JonesFM, et al. (2006) Increased human IgE induced by killing Schistosoma mansoni in vivo is associated with pretreatment Th2 cytokine responsiveness to worm antigens. J Immunol 177 : 5490–5498.
54. JosephS, JonesFM, WalterK, FulfordAJ, KimaniG, et al. (2004) Increases in human T helper 2 cytokine responses to Schistosoma mansoni worm and worm-tegument antigens are induced by treatment with praziquantel. J Infect Dis 190 : 835–842.
55. HaganP, BlumenthalUJ, DunnD, SimpsonAJ, WilkinsHA (1991) Human IgE, IgG4 and resistance to reinfection with Schistosoma haematobium. Nature 349 : 243–245.
56. Bahia-OliveiraLM, GazzinelliG, Eloi-SantosSM, Cunha-MeloJR, Alves-OliveiraLF, et al. (1992) Differential cellular reactivity to adult worm antigens of patients with different clinical forms of schistosomiasis mansoni. Trans R Soc Trop Med Hyg 86 : 57–61.
57. Corrêa-OliveiraR, CaldasIR, GazzinelliG (2000) Natural versus drug-induced resistance in Schistosoma mansoni infection. Parasitol Today 16 : 397–399.
58. VianaIR, Correa-OliveiraR, CarvalhoODS, MassaraCL, ColosimoE, et al. (1995) Comparison of antibody isotype responses to Schistosoma mansoni antigens by infected and putative resistant individuals living in an endemic area. Parasite Immunol 17 : 297–304.
59. BethonyJM, SimonG, DiemertDJ, ParentiD, DesrosiersA, et al. (2008) Randomized, placebo-controlled, double-blind trial of the Na-ASP-2 hookworm vaccine in unexposed adults. Vaccine 26 : 2408–2417.
60. GobertGN, MoertelL, BrindleyPJ, McManusDP (2009) Developmental gene expression profiles of the human pathogen Schistosoma japonicum. BMC Genomics 10 : 128.
61. GobertGN, TranMH, MoertelL, MulvennaJ, JonesMK, et al. (2010) Transcriptional changes in Schistosoma mansoni during early schistosomula development and in the presence of erythrocytes. PLoS Negl Trop Dis 4: e600.
62. YouH, McManusDP, HuW, SmoutMJ, BrindleyPJ, et al. (2013) Transcriptional responses of in vivo praziquantel exposure in schistosomes identifies a functional role for calcium signalling pathway member CamKII. PLoS Pathog 9: e1003254.
63. van BalkomBWM, van GestelRA, BrouwersJFHM, KrijgsveldJ, TielensAGM, et al. (2005) Mass spectrometric analysis of the Schistosoma mansoni tegumental sub-proteome. J Proteome Res 4 : 958–966.
64. TaftAS, YoshinoTP (2011) Cloning and functional characterization of two calmodulin genes during larval development in the parasitic flatworm Schistosoma mansoni. J Parasitol 97 : 72–81.
65. KatsumataT, KohnoS, YamaguchiK, HaraK, AokiY (1989) Hatching of Schistosoma mansoni eggs is a Ca2+/calmodulin-dependent process. Parasitol Res 76 : 90–91.
66. GearyTG, DivoAA, JensenJB (1986) Effect of calmodulin inhibitors on viability and mitochondrial potential of Plasmodium falciparum in culture. Antimicrob Agents Chemother 30 : 785–788.
67. PearsonMS, PickeringDA, McSorleyHJ, BethonyJM, TriboletL, et al. (2012) Enhanced protective efficacy of a chimeric form of the schistosomiasis vaccine antigen Sm-TSP-2. PLoS Negl Trop Dis 6: e1564.
68. DoolanDL, MuY, UnalB, SundareshS, HirstS, et al. (2008) Profiling humoral immune responses to P. falciparum infection with protein microarrays. Proteomics 8 : 4680–4694.
69. CromptonPD, KayalaMA, TraoreB, KayentaoK, OngoibaA, et al. (2010) A prospective analysis of the Ab response to Plasmodium falciparum before and after a malaria season by protein microarray. Proc Natl Acad Sci U S A 107 : 6958–6963.
70. BarryAE, TrieuA, FowkesFJI, PabloJ, Kalantari-DehaghiM, et al. (2011) The stability and complexity of antibody responses to the major surface antigen of Plasmodium falciparum are associated with age in a malaria endemic area. Mol Cell Proteomics 10: M111.008326.
71. TrieuA, KayalaMA, BurkC, MolinaDM, FreilichDA, et al. (2011) Sterile protective immunity to malaria is associated with a panel of novel P. falciparum antigens. Mol Cell Proteomics 10: M111.007948.
72. MutapiF, BurchmoreR, MduluzaT, FoucherA, HarcusY, et al. (2005) Praziquantel treatment of individuals exposed to Schistosoma haematobium enhances serological recognition of defined parasite antigens. J Infect Dis 192 : 1108–1118.
73. MarcillaA, TrelisM, CortésA, SotilloJ, CantalapiedraF, et al. (2012) Extracellular vesicles from parasitic helminths contain specific excretory/secretory proteins and are internalized in intestinal host cells. PLoS One 7: e45974.
74. KariukiTM, Van DamGJ, DeelderAM, FarahIO, YoleDS, et al. (2006) Previous or ongoing schistosome infections do not compromise the efficacy of the attenuated cercaria vaccine. Infect Immun 74 : 3979–3986.
75. YoleDS, PembertonR, ReidGD, WilsonRA (1996) Protective immunity to Schistosoma mansoni induced in the olive baboon Papio anubis by the irradiated cercaria vaccine. Parasitology 112 : 37–46.
76. RollinsonD (2009) A wake up call for urinary schistosomiasis: reconciling research effort with public health importance. Parasitology 136 : 1593–1610.
77. DaviesDH, LiangX, HernandezJE, RandallA, HirstS, et al. (2005) Profiling the humoral immune response to infection by using proteome microarrays: high-throughput vaccine and diagnostic antigen discovery. Proc Natl Acad Sci U S A 102 : 547–552.
78. SundareshS, DoolanDL, HirstS, MuY, UnalB, et al. (2006) Identification of humoral immune responses in protein microarrays using DNA microarray data analysis techniques. Bioinformatics 22 : 1760–1766.
79. Brock G, Pihur V, Datta S, Datta S (2008) clValid, an R package for cluster validation. J Stat Software 25(4).
80. RDC Team (2011) R: a language and environment for statistical computing, reference index version 2.13.0. Vienna: R Foundation for Statistical Computing.
81. ProtasioAV, TsaiIJ, BabbageA, NicholS, HuntM, et al. (2012) A systematically improved high quality genome and transcriptome of the human blood fluke Schistosoma mansoni. PLoS Negl Trop Dis 6: e1455.
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