Discovery of Novel Schistosoma Japonicum Antigens Using a Targeted Protein Microarray Approach

Overview

Journal Parasit Vectors

Publisher Biomed Central

Specialties Parasitology
Tropical Medicine

Date 2014 Jun 27

PMID 24964958

Citations 17

Authors

Hamish E G McWilliam

Patrick Driguez

David Piedrafita

Donald P McManus

Els N T Meeusen

Affiliations

Soon will be listed here.

Abstract

Background: Novel vaccine candidates against Schistosoma japonicum are required, and antigens present in the vulnerable larval developmental stage are attractive targets. Post-genomic technologies are now available which can contribute to such antigen discovery.

Methods: A schistosome-specific protein microarray was probed using the local antibody response against migrating larvae. Antigens were assessed for their novelty and predicted larval expression and host-exposed features. One antigen was further characterised and its sequence and structure were analysed in silico. Real-time polymerase chain reaction was used to analyse transcript expression throughout development, and immunoblotting and enzyme-linked immunosorbent assays employed to determine antigen recognition by antibody samples.

Results: Several known and novel antigens were discovered, two of which showed up-regulated transcription in schistosomula. One novel antigen, termed S. japonicum Ly-6-like protein 1 (Sj-L6L-1), was further characterised and shown to share structural and sequence features with the Ly-6 protein family. It was found to be present in the worm tegument and expressed in both the larval and adult worms, but was found to be antigenic only in the lungs that the larvae migrate to and traverse.

Conclusions: This study represents a novel approach to vaccine antigen discovery and may contribute to schistosome vaccine development against this important group of human and veterinary pathogens.

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References

Gobert G, Moertel L, Brindley P, McManus D . Developmental gene expression profiles of the human pathogen Schistosoma japonicum. BMC Genomics. 2009; 10:128. PMC: 2670322. DOI: 10.1186/1471-2164-10-128. View

Huber W, von Heydebreck A, Sultmann H, Poustka A, Vingron M . Variance stabilization applied to microarray data calibration and to the quantification of differential expression. Bioinformatics. 2002; 18 Suppl 1:S96-104. DOI: 10.1093/bioinformatics/18.suppl_1.s96. View

. The Schistosoma japonicum genome reveals features of host-parasite interplay. Nature. 2009; 460(7253):345-51. PMC: 3747554. DOI: 10.1038/nature08140. View

Driguez P, Doolan D, Loukas A, Felgner P, McManus D . Schistosomiasis vaccine discovery using immunomics. Parasit Vectors. 2010; 3:4. PMC: 2837634. DOI: 10.1186/1756-3305-3-4. View

Bamezai A . Mouse Ly-6 proteins and their extended family: markers of cell differentiation and regulators of cell signaling. Arch Immunol Ther Exp (Warsz). 2004; 52(4):255-66. View

Hockley D, McLaren D . Schistosoma mansoni: changes in the outer membrane of the tegument during development from cercaria to adult worm. Int J Parasitol. 1973; 3(1):13-25. DOI: 10.1016/0020-7519(73)90004-0. View

Hu Y, Lu W, Shen Y, Xu Y, Yuan Z, Zhang C . Immune changes of Schistosoma japonicum infections in various rodent disease models. Exp Parasitol. 2012; 131(2):180-9. DOI: 10.1016/j.exppara.2012.03.022. View

Zhang L, McManus D, Sunderland P, Lu X, Ye J, Loukas A . The cellular distribution and stage-specific expression of two dynein light chains from the human blood fluke Schistosoma japonicum. Int J Biochem Cell Biol. 2005; 37(7):1511-24. DOI: 10.1016/j.biocel.2005.01.015. View

Balloul J, Grzych J, Pierce R, Capron A . A purified 28,000 dalton protein from Schistosoma mansoni adult worms protects rats and mice against experimental schistosomiasis. J Immunol. 1987; 138(10):3448-53. View

10.

Harris A, Russell R, CHARTERS A . A review of schistosomiasis in immigrants in Western Australia, demonstrating the unusual longevity of Schistosoma mansoni. Trans R Soc Trop Med Hyg. 1984; 78(3):385-8. DOI: 10.1016/0035-9203(84)90129-9. View

11.

Cook R, Carvalho-Queiroz C, Wilding G, LoVerde P . Nucleic acid vaccination with Schistosoma mansoni antioxidant enzyme cytosolic superoxide dismutase and the structural protein filamin confers protection against the adult worm stage. Infect Immun. 2004; 72(10):6112-24. PMC: 517585. DOI: 10.1128/IAI.72.10.6112-6124.2004. View

12.

Mulvenna J, Moertel L, Jones M, Nawaratna S, Lovas E, Gobert G . Exposed proteins of the Schistosoma japonicum tegument. Int J Parasitol. 2009; 40(5):543-54. DOI: 10.1016/j.ijpara.2009.10.002. View

13.

Miwa J, Ibanez-Tallon I, Crabtree G, Sanchez R, Sali A, Role L . lynx1, an endogenous toxin-like modulator of nicotinic acetylcholine receptors in the mammalian CNS. Neuron. 1999; 23(1):105-14. DOI: 10.1016/s0896-6273(00)80757-6. View

14.

Roberts S, Macgregor A, Vojvodic M, Wells E, Crabtree J, Wilson R . Tegument surface membranes of adult Schistosoma mansoni: development of a method for their isolation. Mol Biochem Parasitol. 1983; 9(2):105-27. DOI: 10.1016/0166-6851(83)90104-4. View

15.

Sugita Y, Nakano Y, Oda E, Noda K, Tobe T, Miura N . Determination of carboxyl-terminal residue and disulfide bonds of MACIF (CD59), a glycosyl-phosphatidylinositol-anchored membrane protein. J Biochem. 1993; 114(4):473-7. DOI: 10.1093/oxfordjournals.jbchem.a124202. View

16.

McWilliam H, Driguez P, Piedrafita D, Maupin K, Haab B, McManus D . The developing schistosome worms elicit distinct immune responses in different tissue regions. Immunol Cell Biol. 2013; 91(7):477-85. DOI: 10.1038/icb.2013.33. View

17.

Liu S, Cai P, Hou N, Piao X, Wang H, Hung T . Genome-wide identification and characterization of a panel of house-keeping genes in Schistosoma japonicum. Mol Biochem Parasitol. 2012; 182(1-2):75-82. DOI: 10.1016/j.molbiopara.2011.12.007. View

18.

Yang W, Zheng Y, Jones M, McManus D . Molecular characterization of a calponin-like protein from Schistosoma japonicum. Mol Biochem Parasitol. 1999; 98(2):225-37. DOI: 10.1016/s0166-6851(98)00171-6. View

19.

Kelley L, Sternberg M . Protein structure prediction on the Web: a case study using the Phyre server. Nat Protoc. 2009; 4(3):363-71. DOI: 10.1038/nprot.2009.2. View

20.

Han H, Peng J, Hong Y, Zhang M, Han Y, Fu Z . Comparison of the differential expression miRNAs in Wistar rats before and 10 days after S.japonicum infection. Parasit Vectors. 2013; 6:120. PMC: 3640946. DOI: 10.1186/1756-3305-6-120. View