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Advances in vaccine development for human trichuriasis

Published online by Cambridge University Press:  24 March 2021

Jesica Hayon ,
Jill Weatherhead Open the ORCID record for Jill Weatherhead [Opens in a new window] ,
Peter J. Hotez ,
Maria Elena Bottazzi  and
Bin Zhan Open the ORCID record for Bin Zhan [Opens in a new window]
Jesica Hayon
Affiliation:
Department of Medicine, Section of Infectious Diseases, Baylor College of Medicine, Houston, TX, USA
Jill Weatherhead
Affiliation:
Department of Medicine, Section of Infectious Diseases, Baylor College of Medicine, Houston, TX, USA Department of Pediatrics, Section of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA
Peter J. Hotez
Affiliation:
Department of Pediatrics, Section of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA Texas Children's Hospital Center for Vaccine Development, Baylor College of Medicine, Houston, TX77030, USA
Maria Elena Bottazzi
Affiliation:
Department of Pediatrics, Section of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA Texas Children's Hospital Center for Vaccine Development, Baylor College of Medicine, Houston, TX77030, USA
Bin Zhan*
Affiliation:
Department of Pediatrics, Section of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA Texas Children's Hospital Center for Vaccine Development, Baylor College of Medicine, Houston, TX77030, USA
*
Author for correspondence: Bin Zhan, E-mail: bzhan@bcm.edu
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Abstract

Trichuriasis known as whipworm infection caused by Trichuris trichiura, is a highly prevalent soil-transmitted helminthiasis in low- and middle-income countries located in tropical and subtropical areas and affecting approximately 360 million people. Children typically harbour the largest burden of T. trichiura and they are usually co-infected with other soil-transmitted helminth (STH), including Ascaris lumbricoides and hookworm. The consequences of trichuriasis, such as malnutrition and physical and cognitive growth restriction, lead to a massive health burden in endemic regions. Despite the implementation of mass drug administration of anthelminthic treatment to school-age children, T. trichiura infection remains challenging to control due to the low efficacy of current drugs as well as high rates of post-treatment re-infection. Thus, the development of a vaccine that would induce protective immunity and reduce infection rate or community faecal egg output is essential. Hurdles for human whipworm vaccine development include the lack of suitable vaccine antigen targets and animal models for human T. trichiura infection. Instead, rodent whipworm T. muris infected mouse models serve as a major surrogate for testing immunogenicity and efficacy of vaccine candidates. In this review, we summarize recent advances in animal models for T. trichiura antigen discovery and testing of vaccine candidates, while providing an overall view of the current status of T. trichiura vaccine development.

Keywords

Animal modeltrichuriasisTrichuris sppvaccine
Type
Review Article
Information
Parasitology , Volume 148 , Special Issue 14: Lessons from studying roundworm and whipworm in the mouse - common themes and unique features , December 2021 , pp. 1783 - 1794
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Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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References

Adegnika, AA, de Vries, SG, Zinsou, FJ, Honkepehedji, YJ, Dejon Agobe, JC, Vodonou, KG, Bikangui, R, Bouyoukou Hounkpatin, A, Bache, EB, Massinga Loembe, M, van Leeuwen, R, Molemans, M, Kremsner, PG, Yazdanbakhsh, M, Hotez, PJ, Bottazzi, ME, Li, G, Bethony, JM, Diemert, DJ, Grobusch, MP and HookVac, C (2021) Safety and immunogenicity of co-administered hookworm vaccine candidates Na-GST-1 and Na-APR-1 in Gabonese adults: a randomised, controlled, double-blind, phase 1 dose-escalation trial. The Lancet Infectious Diseases 21, 275–285.10.1016/S1473-3099(20)30288-7CrossRefGoogle ScholarPubMed
Bager, P (2013) Use of Trichuris suis ova (TSO) therapy for the treatment of allergy. Arbeiten Aus Dem Paul-ehrlich-institut (bundesinstitut Fur Impfstoffe Und Biomedizinische Arzneimittel) Langen/hessen 97, 128–129.Google ScholarPubMed
Bager, P, Arnved, J, Ronborg, S, Wohlfahrt, J, Poulsen, LK, Westergaard, T, Petersen, HW, Kristensen, B, Thamsborg, S, Roepstorff, A, Kapel, C and Melbye, M (2010) Trichuris suis ova therapy for allergic rhinitis: a randomized, double-blind, placebo-controlled clinical trial. Journal of Allergy and Clinical Immunology 125, 123–130 e121–e123.10.1016/j.jaci.2009.08.006CrossRefGoogle ScholarPubMed
Bancroft, AJ, McKenzie, AN and Grencis, RK (1998) A critical role for IL-13 in resistance to intestinal nematode infection. Journal of Immunology 160, 3453–3461.Google ScholarPubMed
Bancroft, AJ, Artis, D, Donaldson, DD, Sypek, JP and Grencis, RK (2000) Gastrointestinal nematode expulsion in IL-4 knockout mice is IL-13 dependent. European Journal of Immunology 30, 2083–2091.10.1002/1521-4141(200007)30:7<2083::AID-IMMU2083>3.0.CO;2-33.0.CO;2-3>CrossRefGoogle ScholarPubMed
Bancroft, AJ, Else, KJ, Humphreys, NE and Grencis, RK (2001) The effect of challenge and trickle Trichuris muris infections on the polarisation of the immune response. International Journal for Parasitology 31, 1627–1637.10.1016/S0020-7519(01)00281-8CrossRefGoogle ScholarPubMed
Bancroft, AJ, Levy, CW, Jowitt, TA, Hayes, KS, Thompson, S, McKenzie, EA, Ball, MD, Dubaissi, E, France, AP, Bellina, B, Sharpe, C, Mironov, A, Brown, SL, Cook, PC, MacDonald, AS, Thornton, DJ and Grencis, RK (2019) The major secreted protein of the whipworm parasite tethers to matrix and inhibits interleukin-13 function. Nature Communications 10, 2344. doi: 10.1038/s41467-019-09996-z.CrossRefGoogle ScholarPubMed
Barker, GC and Bundy, DA (1999) Isolation of a gene family that encodes the porin-like proteins from the human parasitic nematode Trichuris trichiura. Gene 229, 131–136.10.1016/S0378-1119(99)00039-6CrossRefGoogle ScholarPubMed
Bartsch, SM, Hotez, PJ, Hertenstein, DL, Diemert, DJ, Zapf, KM, Bottazzi, ME, Bethony, JM, Brown, ST and Lee, BY (2016) Modeling the economic and epidemiologic impact of hookworm vaccine and mass drug administration (MDA) in Brazil, a high transmission setting. Vaccine 34, 2197–2206.10.1016/j.vaccine.2016.03.018CrossRefGoogle ScholarPubMed
Beer, RJ (1976) The relationship between Trichuris trichiura (Linnaeus 1758) of man and Trichuris suis (Schrank 1788) of the pig. Research in Veterinary Science 20, 47–54.10.1016/S0034-5288(18)33478-7CrossRefGoogle ScholarPubMed
Bellaby, T, Robinson, K and Wakelin, D (1996) Induction of differential T-helper-cell responses in mice infected with variants of the parasitic nematode Trichuris muris. Infection and Immunity 64, 791–795.10.1128/iai.64.3.791-795.1996CrossRefGoogle ScholarPubMed
Bottazzi, ME (2015) The human hookworm vaccine: recent updates and prospects for success. Journal of Helminthology 89, 540–544.CrossRefGoogle Scholar
Bourke, CD, Mutapi, F, Nausch, N, Photiou, DM, Poulsen, LK, Kristensen, B, Arnved, J, Ronborg, S, Roepstorff, A, Thamsborg, S, Kapel, C, Melbye, M and Bager, P (2012) Trichuris suis ova therapy for allergic rhinitis does not affect allergen-specific cytokine responses despite a parasite-specific cytokine response. Clinical and Experimental Allergy 42, 1582–1595.10.1111/j.1365-2222.2012.04063.xCrossRefGoogle Scholar
Briggs, N, Wei, J, Versteeg, L, Zhan, B, Keegan, B, Damania, A, Pollet, J, Hayes, KS, Beaumier, C, Seid, CA, Leong, J, Grencis, RK, Bottazzi, ME, Sastry, KJ and Hotez, PJ (2018) Trichuris muris whey acidic protein induces type 2 protective immunity against whipworm. PLoS Pathogens 14, e1007273.CrossRefGoogle ScholarPubMed
Brooker, S, Hotez, PJ and Bundy, DA (2008) Hookworm-related anaemia among pregnant women: a systematic review. PLoS Neglected Tropical Diseases 2, e291.10.1371/journal.pntd.0000291CrossRefGoogle ScholarPubMed
Bundy, DA, Cooper, ES, Thompson, DE, Anderson, RM and Didier, JM (1987) Age-related prevalence and intensity of Trichuris trichiura infection in a St. Lucian community. Transactions of the Royal Society of Tropical Medicine and Hygiene 81, 85–94.10.1016/0035-9203(87)90293-8CrossRefGoogle Scholar
Clarke, NE, Doi, SAR, Wangdi, K, Chen, Y, Clements, ACA and Nery, SV (2019) Efficacy of anthelminthic drugs and drug combinations against soil-transmitted helminths: a systematic review and network meta-analysis. Clinical Infectious Diseases 68, 96–105.Google ScholarPubMed
Cliffe, LJ and Grencis, RK (2004) The Trichuris muris system: a paradigm of resistance and susceptibility to intestinal nematode infection. Advances in Parasitology 57, 255–307.10.1016/S0065-308X(04)57004-5CrossRefGoogle ScholarPubMed
D'Elia, R, Behnke, JM, Bradley, JE and Else, KJ (2009) Regulatory T cells: a role in the control of helminth-driven intestinal pathology and worm survival. Journal of Immunology 182, 2340–2348.10.4049/jimmunol.0802767CrossRefGoogle ScholarPubMed
Demiri, M, Muller-Luda, K, Agace, WW and Svensson-Frej, M (2017) Distinct DC subsets regulate adaptive Th1 and 2 responses during Trichuris muris infection. Parasite Immunology 39. doi: 10.1111/pim.12458.CrossRefGoogle ScholarPubMed
Despommier, DD and Muller, M (1976) The stichosome and its secretion granules in the mature muscle larva of Trichinella spiralis. Journal of Parasitology 62, 775–785.10.2307/3278960CrossRefGoogle ScholarPubMed
Diemert, DJ, Bottazzi, ME, Plieskatt, J, Hotez, PJ and Bethony, JM (2018) Lessons along the critical path: developing vaccines against human helminths. Trends in Parasitology 34, 747–758.10.1016/j.pt.2018.07.005CrossRefGoogle ScholarPubMed
Dixon, H, Johnston, CE and Else, KJ (2008) Antigen selection for future anti-Trichuris vaccines: a comparison of cytokine and antibody responses to larval and adult antigen in a primary infection. Parasite Immunology 30, 454–461.10.1111/j.1365-3024.2008.01035.xCrossRefGoogle Scholar
Dixon, H, Little, MC and Else, KJ (2010) Characterisation of the protective immune response following subcutaneous vaccination of susceptible mice against Trichuris muris. International Journal for Parasitology 40, 683–693.10.1016/j.ijpara.2009.11.008CrossRefGoogle ScholarPubMed
Drake, L, Korchev, Y, Bashford, L, Djamgoz, M, Wakelin, D, Ashall, F and Bundy, D (1994) The major secreted product of the whipworm, Trichuris, is a pore-forming protein. Proceedings of the Biological Sciences 257, 255–261.Google ScholarPubMed
Drake, LJ, Barker, GC, Korchev, Y, Lab, M, Brooks, H and Bundy, DA (1998) Molecular and functional characterization of a recombinant protein of Trichuris trichiura. Proceedings of the Biological Sciences 265, 1559–1565.CrossRefGoogle ScholarPubMed
Eichenberger, RM, Talukder, MH, Field, MA, Wangchuk, P, Giacomin, P, Loukas, A and Sotillo, J (2018) Characterization of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host-parasite communication. Journal of Extracellular Vesicles 7, 1428004.CrossRefGoogle ScholarPubMed
Else, K and Wakelin, D (1988) The effects of H-2 and non-H-2 genes on the expulsion of the nematode Trichuris muris from inbred and congenic mice. Parasitology 96(Pt 3), 543–550.CrossRefGoogle ScholarPubMed
Else, KJ and Wakelin, D (1990) Genetically-determined influences on the ability of poor responder mice to respond to immunization against Trichuris muris. Parasitology 100(Pt 3), 479–489.10.1017/S0031182000078793CrossRefGoogle ScholarPubMed
Else, KJ, Wakelin, D and Roach, TI (1989) Host predisposition to trichuriasis: the mouse – T. muris model. Parasitology 98(Pt 2), 275–282.10.1017/S0031182000062193CrossRefGoogle ScholarPubMed
Else, KJ, Hultner, L and Grencis, RK (1992) Modulation of cytokine production and response phenotypes in murine trichuriasis. Parasite Immunology 14, 441–449.10.1111/j.1365-3024.1992.tb00018.xCrossRefGoogle ScholarPubMed
Else, KJ, Finkelman, FD, Maliszewski, CR and Grencis, RK (1994) Cytokine-mediated regulation of chronic intestinal helminth infection. Journal of Experimental Medicine 179, 347–351.CrossRefGoogle ScholarPubMed
Else, KJ, Keiser, J, Holland, CV, Grencis, RK, Sattelle, DB, Fujiwara, RT, Bueno, LL, Asaolu, SO, Sowemimo, OA and Cooper, PJ (2020) Whipworm and roundworm infections. Nature Reviews Disease Primers 6, 44.10.1038/s41572-020-0171-3CrossRefGoogle ScholarPubMed
Entwistle, LJ and Wilson, MS (2017) MicroRNA-mediated regulation of immune responses to intestinal helminth infections. Parasite Immunology 39. doi: 10.1111/pim.12406.CrossRefGoogle ScholarPubMed
Foth, BJ, Tsai, IJ, Reid, AJ, Bancroft, AJ, Nichol, S, Tracey, A, Holroyd, N, Cotton, JA, Stanley, EJ, Zarowiecki, M, Liu, JZ, Huckvale, T, Cooper, PJ, Grencis, RK and Berriman, M (2014) Whipworm genome and dual-species transcriptome analyses provide molecular insights into an intimate host-parasite interaction. Nature Genetics 46, 693–700.10.1038/ng.3010CrossRefGoogle ScholarPubMed
Gaherwal, S and Prakash, M (2011) Lymphocyte migration inhibition response in Trichuris muris infected and vaccinated mice. Iranian Journal of Parasitology 6, 34–40.Google ScholarPubMed
Geary, TG (2012) Are new anthelmintics needed to eliminate human helminthiases? Current Opinion in Infectious Diseases 25, 709–717.10.1097/QCO.0b013e328359f04aCrossRefGoogle ScholarPubMed
Ghai, RR, Simons, ND, Chapman, CA, Omeja, PA, Davies, TJ, Ting, N and Goldberg, TL (2014) Hidden population structure and cross-species transmission of whipworms (Trichuris sp.) in humans and non-human primates in Uganda. PLoS Neglected Tropical Diseases 8, e3256.10.1371/journal.pntd.0003256CrossRefGoogle ScholarPubMed
Gomez-Samblas, M, Garcia-Rodriguez, JJ, Trelis, M, Bernal, D, Lopez-Jaramillo, FJ, Santoyo-Gonzalez, F, Vilchez, S, Espino, AM, Bolas-Fernandez, F and Osuna, A (2017) Self-adjuvanting C18 lipid vinil sulfone-PP2A vaccine: study of the induced immunomodulation against Trichuris muris infection. Open Biology 7, 170031. doi: 10.1098/rsob.170031CrossRefGoogle ScholarPubMed
Grencis, RK and Entwistle, GM (1997) Production of an interferon-gamma homologue by an intestinal nematode: functionally significant or interesting artefact? Parasitology 115(Suppl), S101–S106.10.1017/S0031182097002114CrossRefGoogle ScholarPubMed
Hansen, EP, Kringel, H, Williams, AR and Nejsum, P (2015) Secretion of RNA-containing extracellular vesicles by the porcine whipworm, Trichuris suis. Journal of Parasitology 101, 336–340.10.1645/14-714.1CrossRefGoogle ScholarPubMed
Hasnain, SZ, Evans, CM, Roy, M, Gallagher, AL, Kindrachuk, KN, Barron, L, Dickey, BF, Wilson, MS, Wynn, TA, Grencis, RK and Thornton, DJ (2011) Muc5ac: a critical component mediating the rejection of enteric nematodes. Journal of Experimental Medicine 208, 893–900.10.1084/jem.20102057CrossRefGoogle ScholarPubMed
Hayes, KS, Bancroft, AJ and Grencis, RK (2007) The role of TNF-alpha in Trichuris muris infection II: global enhancement of ongoing Th1 or Th2 responses. Parasite Immunology 29, 583–594.10.1111/j.1365-3024.2007.00980.xCrossRefGoogle ScholarPubMed
Hayes, KS, Hager, R and Grencis, RK (2014) Sex-dependent genetic effects on immune responses to a parasitic nematode. BMC Genomics 15, 193.10.1186/1471-2164-15-193CrossRefGoogle ScholarPubMed
He, H, Liu, D, Lin, H, Jiang, S, Ying, Y, Chun, S, Deng, H, Zaia, J, Wen, R and Luo, Z (2016) Phosphatidylethanolamine binding protein 4 (PEBP4) is a secreted protein and has multiple functions. Biochimica et Biophysica Acta 1863, 1682–1689.10.1016/j.bbamcr.2016.03.022CrossRefGoogle ScholarPubMed
Helmby, H, Takeda, K, Akira, S and Grencis, RK (2001) Interleukin (IL)-18 promotes the development of chronic gastrointestinal helminth infection by downregulating IL-13. Journal of Experimental Medicine 194, 355–364.10.1084/jem.194.3.355CrossRefGoogle ScholarPubMed
Hepworth, MR and Grencis, RK (2009) Disruption of Th2 immunity results in a gender-specific expansion of IL-13 producing accessory NK cells during helminth infection. Journal of Immunology 183, 3906–3914.10.4049/jimmunol.0900577CrossRefGoogle Scholar
Hepworth, MR, Hardman, MJ and Grencis, RK (2010) The role of sex hormones in the development of Th2 immunity in a gender-biased model of Trichuris muris infection. European Journal of Immunology 40, 406–416.10.1002/eji.200939589CrossRefGoogle Scholar
Hotez, PJ (2018 a) The global fight to develop antipoverty vaccines in the anti-vaccine era. Human Vaccines & Immunotherapeutics 14, 2128–2131.10.1080/21645515.2018.1430542CrossRefGoogle ScholarPubMed
Hotez, PJ (2018 b) Human parasitology and parasitic diseases: heading towards 2050. Advances in Parasitology 100, 29–38.10.1016/bs.apar.2018.03.002CrossRefGoogle ScholarPubMed
Hotez, P (2019) America and Europe's new normal: the return of vaccine-preventable diseases. Pediatric Research 85, 912–914.10.1038/s41390-019-0354-3CrossRefGoogle ScholarPubMed
Hotez, PJ, Bethony, JM, Oliveira, SC, Brindley, PJ and Loukas, A (2008 a) Multivalent anthelminthic vaccine to prevent hookworm and schistosomiasis. Expert Review of Vaccines 7, 745–752.10.1586/14760584.7.6.745CrossRefGoogle ScholarPubMed
Hotez, PJ, Brindley, PJ, Bethony, JM, King, CH, Pearce, EJ and Jacobson, J (2008 b) Helminth infections: the great neglected tropical diseases. Journal of Clinical Investigation 118, 1311–1321.10.1172/JCI34261CrossRefGoogle ScholarPubMed
Hotez, PJ, Alvarado, M, Basanez, MG, Bolliger, I, Bourne, R, Boussinesq, M, Brooker, SJ, Brown, AS, Buckle, G, Budke, CM, Carabin, H, Coffeng, LE, Fevre, EM, Furst, T, Halasa, YA, Jasrasaria, R, Johns, NE, Keiser, J, King, CH, Lozano, R, Murdoch, ME, O'Hanlon, S, Pion, SD, Pullan, RL, Ramaiah, KD, Roberts, T, Shepard, DS, Smith, JL, Stolk, WA, Undurraga, EA, Utzinger, J, Wang, M, Murray, CJ and Naghavi, M (2014) The global burden of disease study 2010: interpretation and implications for the neglected tropical diseases. PLoS Neglected Tropical Diseases 8, e2865.CrossRefGoogle ScholarPubMed
Huang, X, Zeng, LR, Chen, FS, Zhu, JP and Zhu, MH (2018) Trichuris suis ova therapy in inflammatory bowel disease: a meta-analysis. Medicine (Baltimore) 97, e12087.10.1097/MD.0000000000012087CrossRefGoogle ScholarPubMed
IHME (2019) The Global Burden of Trichuriasis in 2019. IHME. http://www.healthdata.org/results/gbd_summaries/2019/trichuriasis-level-4-cause.Google Scholar
James, SL and Nacy, C (1993) Effector functions of activated macrophages against parasites. Current Opinion in Immunology 5, 518–523.10.1016/0952-7915(93)90032-NCrossRefGoogle ScholarPubMed
Janssens, V and Goris, J (2001) Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling. Biochemical Journal 353, 417–439.10.1042/bj3530417CrossRefGoogle ScholarPubMed
Jenkins, SN and Wakelin, D (1977) The source and nature of some functional antigens of Trichuris muris. Parasitol ogy 74, 153–161. https://doi.org/10.1017/S0031182000047648.CrossRefGoogle Scholar
Jenkins, SN and Wakelin, D (1983) Functional antigens of Trichuris muris released during in vitro maintenance: their immunogenicity and partial purification. Parasitology 86(Pt 1), 73–82.10.1017/S0031182000057188CrossRefGoogle ScholarPubMed
Jourdan, PM, Lamberton, PHL, Fenwick, A and Addiss, DG (2018) Soil-transmitted helminth infections. Lancet (London, England) 391, 252–265.CrossRefGoogle ScholarPubMed
Jouvin, MH and Kinet, JP (2012) Trichuris suis ova: testing a helminth-based therapy as an extension of the hygiene hypothesis. Journal of Allergy and Clinical Immunology 130, 3–10; quiz 11–12.10.1016/j.jaci.2012.05.028CrossRefGoogle ScholarPubMed
Keenan, JD, Hotez, PJ, Amza, A, Stoller, NE, Gaynor, BD, Porco, TC and Lietman, TM (2013) Elimination and eradication of neglected tropical diseases with mass drug administrations: a survey of experts. PLoS Neglected Tropical Diseases 7, e2562.CrossRefGoogle ScholarPubMed
Keiser, J and Utzinger, J (2008) Efficacy of current drugs against soil-transmitted helminth infections: systematic review and meta-analysis. JAMA 299, 1937–1948.10.1001/jama.299.16.1937CrossRefGoogle ScholarPubMed
Keller, L, Palmeirim, MS, Ame, SM, Ali, SM, Puchkov, M, Huwyler, J, Hattendorf, J and Keiser, J (2020) Efficacy and safety of ascending dosages of moxidectin and moxidectin-albendazole against Trichuris trichiura in adolescents: a randomized controlled trial. Clinical Infectious Diseases 70, 1193–1201.Google ScholarPubMed
Khan, WI, Richard, M, Akiho, H, Blennerhasset, PA, Humphreys, NE, Grencis, RK, Van Snick, J and Collins, SM (2003) Modulation of intestinal muscle contraction by interleukin-9 (IL-9) or IL-9 neutralization: correlation with worm expulsion in murine nematode infections. Infection and Immunity 71, 2430–2438.10.1128/IAI.71.5.2430-2438.2003CrossRefGoogle ScholarPubMed
Khuroo, MS, Khuroo, MS and Khuroo, NS (2010) Trichuris dysentery syndrome: a common cause of chronic iron deficiency anemia in adults in an endemic area (with videos). Gastrointestinal Endoscopy 71, 200–204.10.1016/j.gie.2009.08.002CrossRefGoogle Scholar
Klementowicz, JE, Travis, MA and Grencis, RK (2012) Trichuris muris: a model of gastrointestinal parasite infection. Seminars in Immunopathology 34, 815–828.10.1007/s00281-012-0348-2CrossRefGoogle Scholar
Koyama, K and Ito, Y (1996) Comparative studies on immune responses to infection in susceptible B10.BR mice infected with different strains of the murine nematode parasite Trichuris muris. Parasite Immunology 18, 257–263.10.1046/j.1365-3024.1996.d01-92.xCrossRefGoogle ScholarPubMed
Lee, TD, Grencis, RK and Wakelin, D (1982) Specific cross-immunity between Trichinella spiralis and Trichuris muris: immunization with heterologous infections and antigens and transfer of immunity with heterologous immune mesenteric lymph node cells. Parasitology 84, 381–389.10.1017/S0031182000044929CrossRefGoogle ScholarPubMed
Leroux, LP, Nasr, M, Valanparambil, R, Tam, M, Rosa, BA, Siciliani, E, Hill, DE, Zarlenga, DS, Jaramillo, M, Weinstock, JV, Geary, TG, Stevenson, MM, Urban, JF Jr., Mitreva, M and Jardim, A (2018) Analysis of the Trichuris suis excretory/secretory proteins as a function of life cycle stage and their immunomodulatory properties. Scientific Reports 8, 15921.10.1038/s41598-018-34174-4CrossRefGoogle ScholarPubMed
Lillywhite, JE, Cooper, ES, Needham, CS, Venugopal, S, Bundy, DA and Bianco, AE (1995) Identification and characterization of excreted/secreted products of Trichuris trichiura. Parasite Immunology 17, 47–54.10.1111/j.1365-3024.1995.tb00965.xCrossRefGoogle ScholarPubMed
Liu, Z, Kelleher, A, Tabb, S, Wei, J, Pollet, J, Hotez, PJ, Bottazzi, ME, Zhan, B and Asojo, OA (2017) Identification, characterization, and structure of Tm16 from Trichuris muris. Journal of Parasitology Research 2017, 4342789.10.1155/2017/4342789CrossRefGoogle ScholarPubMed
McCarty, TR, Turkeltaub, JA and Hotez, PJ (2014) Global progress towards eliminating gastrointestinal helminth infections. Current Opinion in Gastroenterology 30, 18–24.CrossRefGoogle ScholarPubMed
McSorley, HJ and Maizels, RM (2012) Helminth infections and host immune regulation. Clinical Microbiology Reviews 25, 585–608.10.1128/CMR.05040-11CrossRefGoogle ScholarPubMed
Mohamed Fawzi, E, Cruz Bustos, T, Gomez Samblas, M, Gonzalez-Gonzalez, G, Solano, J, Gonzalez-Sanchez, ME, De Pablos, LM, Corral-Caridad, MJ, Cuquerella, M, Osuna, A and Alunda, JM (2013) Intranasal immunization of lambs with serine/threonine phosphatase 2A against gastrointestinal nematodes. Clinical and Vaccine Immunology 20, 1352–1359.10.1128/CVI.00336-13CrossRefGoogle ScholarPubMed
Nejsum, P, Betson, M, Bendall, RP, Thamsborg, SM and Stothard, JR (2012) Assessing the zoonotic potential of Ascaris suum and Trichuris suis: looking to the future from an analysis of the past. Journal of Helminthology 86, 148–155.CrossRefGoogle Scholar
Palmeirim, MS, Hurlimann, E, Knopp, S, Speich, B, Belizario, V Jr., Joseph, SA, Vaillant, M, Olliaro, P and Keiser, J (2018) Efficacy and safety of co-administered ivermectin plus albendazole for treating soil-transmitted helminths: a systematic review, meta-analysis and individual patient data analysis. PLoS Neglected Tropical Diseases 12, e0006458.10.1371/journal.pntd.0006458CrossRefGoogle ScholarPubMed
Patel, N, Kreider, T, Urban, JF Jr. and Gause, WC (2009). Characterisation of effector mechanisms at the host:parasite interface during the immune response to tissue-dwelling intestinal nematode parasites. International Journal for Parasitology 39, 13–21.10.1016/j.ijpara.2008.08.003CrossRefGoogle ScholarPubMed
Patel, C, Coulibaly, JT, Schulz, JD, N'Gbesso, Y, Hattendorf, J and Keiser, J (2020) Efficacy and safety of ascending dosages of albendazole against Trichuris trichiura in preschool-aged children, school-aged children and adults: a multi-cohort randomized controlled trial. EClinicalMedicine 22, 100335.10.1016/j.eclinm.2020.100335CrossRefGoogle ScholarPubMed
Polack, FP, Thomas, SJ, Kitchin, N, Absalon, J, Gurtman, A, Lockhart, S, Perez, JL, Perez Marc, G, Moreira, ED, Zerbini, C, Bailey, R, Swanson, KA, Roychoudhury, S, Koury, K, Li, P, Kalina, WV, Cooper, D, Frenck, RW Jr., Hammitt, LL, Tureci, O, Nell, H, Schaefer, A, Unal, S, Tresnan, DB, Mather, S, Dormitzer, PR, Sahin, U, Jansen, KU and Gruber, WC and Group CCT (2020). Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. New England Journal of Medicine 383, 2603–2615.10.1056/NEJMoa2034577CrossRefGoogle ScholarPubMed
Pullan, RL, Smith, JL, Jasrasaria, R and Brooker, SJ (2014) Global numbers of infection and disease burden of soil transmitted helminth infections in 2010. Parasites & Vectors 7, 37.CrossRefGoogle ScholarPubMed
Radoslavov, G, Jordanova, R, Teofanova, D, Georgieva, K, Hristov, P, Salomone-Stagni, M, Liebau, E and Bankov, I (2010) A novel secretory poly-cysteine and histidine-tailed metalloprotein (Ts-PCHTP) from Trichinella spiralis (Nematoda). PLoS One 5, e13343.10.1371/journal.pone.0013343CrossRefGoogle Scholar
Rao, KV, Chen, L, Gnanasekar, M and Ramaswamy, K (2002) Cloning and characterization of a calcium-binding, histamine-releasing protein from Schistosoma mansoni. Journal of Biological Chemistry 277, 31207–31213.10.1074/jbc.M204114200CrossRefGoogle ScholarPubMed
Rhee, JH, Lee, SE and Kim, SY (2012) Mucosal vaccine adjuvants update. Clinical and Experimental Vaccine Research 1, 50–63.10.7774/cevr.2012.1.1.50CrossRefGoogle ScholarPubMed
Richard, M, Grencis, RK, Humphreys, NE, Renauld, JC and Van Snick, J (2000) Anti-IL-9 vaccination prevents worm expulsion and blood eosinophilia in Trichuris muris-infected mice. Proceedings of the National Academy of Sciences of the United States of America 97, 767–772.CrossRefGoogle ScholarPubMed
Robinson, K, Bellaby, T and Wakelin, D (1995) Efficacy of oral vaccination against the murine intestinal parasite Trichuris muris is dependent upon host genetics. Infection and Immunity 63, 1762–1766.10.1128/iai.63.5.1762-1766.1995CrossRefGoogle ScholarPubMed
Santos, LN, Gallo, MB, Silva, ES, Figueiredo, CA, Cooper, PJ, Barreto, ML, Loureiro, S, Pontes-de-Carvalho, LC and Alcantara-Neves, NM (2013) A proteomic approach to identify proteins from Trichuris trichiura extract with immunomodulatory effects. Parasite Immunology 35, 188–193.10.1111/pim.12025CrossRefGoogle ScholarPubMed
Seki, M, Matsura, R, Iwamori, T, Nukumi, N, Yamanouchi, K, Kano, K, Naito, K and Tojo, H (2012) Identification of whey acidic protein (WAP) in dog milk. Experimental Animals 61, 67–70.10.1538/expanim.61.67CrossRefGoogle Scholar
Shears, RK, Bancroft, AJ, Hughes, GW, Grencis, RK and Thornton, DJ (2018) Extracellular vesicles induce protective immunity against Trichuris muris. Parasite Immunology 40, e12536.10.1111/pim.12536CrossRefGoogle ScholarPubMed
Singh, PK, Kushwaha, S, Rana, AK and Misra-Bhattacharya, S (2014) Cofactor independent phosphoglycerate mutase of Brugia malayi induces a mixed Th1/Th2 type immune response and inhibits larval development in the host. Biomedical Research International 2014, 590281.10.1155/2014/590281CrossRefGoogle ScholarPubMed
Solano-Parada, J, Gonzalez-Gonzalez, G, Torro, LM, dos Santos, MF, Espino, AM, Burgos, M and Osuna, A (2010) Effectiveness of intranasal vaccination against Angiostrongylus costaricensis using a serine/threonine phosphatase 2 A synthetic peptide and recombinant antigens. Vaccine 28, 5185–5196.10.1016/j.vaccine.2010.05.072CrossRefGoogle ScholarPubMed
Soukhathammavong, PA, Sayasone, S, Phongluxa, K, Xayaseng, V, Utzinger, J, Vounatsou, P, Hatz, C, Akkhavong, K, Keiser, J and Odermatt, P (2012) Low efficacy of single-dose albendazole and mebendazole against hookworm and effect on concomitant helminth infection in Lao PDR. PLoS Neglected Tropical Diseases 6, e1417.10.1371/journal.pntd.0001417CrossRefGoogle ScholarPubMed
Stephenson, LS, Holland, CV and Cooper, ES (2000) The public health significance of Trichuris trichiura. Parasitology 121(Suppl), S73–S95.10.1017/S0031182000006867CrossRefGoogle ScholarPubMed
Summers, RW, Elliott, DE, Urban, JF Jr., Thompson, R and Weinstock, JV (2005 a) Trichuris suis therapy in Crohn's disease. Gut 54, 87–90.10.1136/gut.2004.041749CrossRefGoogle ScholarPubMed
Summers, RW, Elliott, DE, Urban, JF Jr., Thompson, RA and Weinstock, JV (2005 b) Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology 128, 825–832.10.1053/j.gastro.2005.01.005CrossRefGoogle ScholarPubMed
Tan, TH, Edgerton, SA, Kumari, R, McAlister, MS, Roe, SM, Nagl, S, Pearl, LH, Selkirk, ME, Bianco, AE, Totty, NF, Engwerda, C, Gray, CA and Meyer, DJ (2001) Macrophage migration inhibitory factor of the parasitic nematode Trichinella spiralis. Biochemical Journal 357, 373–383.10.1042/bj3570373CrossRefGoogle ScholarPubMed
Tang, F, Xu, L, Yan, R, Song, X and Li, X (2012) Evaluation of the immune response induced by DNA vaccines expressing MIF and MCD-1 genes of Trichinella spiralis in BALB/c mice. Journal of Helminthology 86, 430–439.10.1017/S0022149X11000654CrossRefGoogle ScholarPubMed
Tang, F, Xu, L, Yan, R, Song, X and Li, X (2013) A DNA vaccine co-expressing Trichinella spiralis MIF and MCD-1 with murine ubiquitin induces partial protective immunity in mice. Journal of Helminthology 87, 24–33.10.1017/S0022149X1100068XCrossRefGoogle ScholarPubMed
Taylor, MD and Else, KJ (2002) Human Trichuris-specific antibody responses in vaccinated hu-PBL-SCID mice. Parasite Immunology 24, 1–13.10.1046/j.0141-9838.2001.00435.xCrossRefGoogle ScholarPubMed
Tritten, L, Tam, M, Vargas, M, Jardim, A, Stevenson, MM, Keiser, J and Geary, TG (2017) Excretory/secretory products from the gastrointestinal nematode Trichuris muris. Experimental Parasitology 178, 30–36.10.1016/j.exppara.2017.05.003CrossRefGoogle ScholarPubMed
VandeBerg, JL and Williams-Blangero, S (1997) Advantages and limitations of nonhuman primates as animal models in genetic research on complex diseases. Journal of Medical Primatology 26, 113–119.10.1111/j.1600-0684.1997.tb00042.xCrossRefGoogle ScholarPubMed
Vercruysse, J, Albonico, M, Behnke, JM, Kotze, AC, Prichard, RK, McCarthy, JS, Montresor, A and Levecke, B (2011) Is anthelmintic resistance a concern for the control of human soil-transmitted helminths? International Journal for Parasitology. Drugs and Drug Resistance 1, 14–27.10.1016/j.ijpddr.2011.09.002CrossRefGoogle ScholarPubMed
Versteeg, L, Almutairi, MM, Hotez, PJ and Pollet, J (2019) Enlisting the mRNA vaccine platform to combat parasitic infections. Vaccines (Basel) 7, 122. doi: 10.3390/vaccines7040122CrossRefGoogle ScholarPubMed
Voldsgaard, A, Bager, P, Garde, E, Akeson, P, Leffers, AM, Madsen, CG, Kapel, C, Roepstorff, A, Thamsborg, SM, Melbye, M, Siebner, H, Sondergaard, HB, Sellebjerg, F and Sorensen, PS (2015) Trichuris suis ova therapy in relapsing multiple sclerosis is safe but without signals of beneficial effect. Multiple Sclerosis 21, 1723–1729.10.1177/1352458514568173CrossRefGoogle ScholarPubMed
Wakelin, D and Selby, GR (1973) Functional antigens of Trichuris muris. The stimulation of immunity by vaccination of mice with somatic antigen preparations. International Journal for Parasitology 3, 711–715.10.1016/0020-7519(73)90061-1CrossRefGoogle ScholarPubMed
Wakelin, D, Farias, SE and Bradley, JE (2002) Variation and immunity to intestinal worms. Parasitology 125(Suppl), S39–S50.10.1017/S0031182002001440CrossRefGoogle ScholarPubMed
Wangchuk, P, Kouremenos, K, Eichenberger, RM, Pearson, M, Susianto, A, Wishart, DS, McConville, MJ and Loukas, A (2019) Metabolomic profiling of the excretory-secretory products of hookworm and whipworm. Metabolomics 15, 101.10.1007/s11306-019-1561-yCrossRefGoogle ScholarPubMed
Weatherhead, JE and Hotez, PJ (2015). Worm infections in children. Pediatrics in Review 36, 341–352; quiz 353–344.CrossRefGoogle ScholarPubMed
WHO (2006) Preventive Chemotherapy in Human Helminthiasis: Coordinated Use of Anthelmintic Drugs in Control Interventions: A Manual for Health Professionals and Programme Managers. Geneva, Switzerland: World Health Organization Press, p74.Google Scholar
Williams, IR (2006) CCR6 and CCL20: partners in intestinal immunity and lymphorganogenesis. Annals of the New York Academy of Sciences 1072, 52–61.10.1196/annals.1326.036CrossRefGoogle ScholarPubMed
Xie, Y, Zhao, B, Hoberg, EP, Li, M, Zhou, X, Gu, X, Lai, W, Peng, X and Yang, G (2018) Genetic characterisation and phylogenetic status of whipworms (Trichuris spp.) from captive non-human primates in China, determined by nuclear and mitochondrial sequencing. Parasites & Vectors 11, 516.10.1186/s13071-018-3100-5CrossRefGoogle ScholarPubMed
Yap, P, Du, ZW, Wu, FW, Jiang, JY, Chen, R, Zhou, XN, Hattendorf, J, Utzinger, J and Steinmann, P (2013) Rapid re-infection with soil-transmitted helminths after triple-dose albendazole treatment of school-aged children in Yunnan, People's Republic of China. American Journal of Tropical Medicine and Hygiene 89, 23–31.10.4269/ajtmh.13-0009CrossRefGoogle Scholar
Zawawi, A and Else, KJ (2020) Soil-transmitted helminth vaccines: are we getting closer? Frontiers in Immunology 11, 576748.10.3389/fimmu.2020.576748CrossRefGoogle ScholarPubMed
Zawawi, A, Forman, R, Smith, H, Mair, I, Jibril, M, Albaqshi, MH, Brass, A, Derrick, JP and Else, KJ (2020) In silico design of a T-cell epitope vaccine candidate for parasitic helminth infection. PLoS Pathogens 16, e1008243.10.1371/journal.ppat.1008243CrossRefGoogle ScholarPubMed
Zeehaida, M, Zueter, A, Zairi, NZ and Zunulhisham, S (2015) Trichuris dysentery syndrome: do we learn enough from case studies? Tropical Biomedicine 32, 545–550.Google ScholarPubMed
Zhan, B, Perally, S, Brophy, PM, Xue, J, Goud, G, Liu, S, Deumic, V, de Oliveira, LM, Bethony, J, Bottazzi, ME, Jiang, D, Gillespie, P, Xiao, SH, Gupta, R, Loukas, A, Ranjit, N, Lustigman, S, Oksov, Y and Hotez, P (2010) Molecular cloning, biochemical characterization, and partial protective immunity of the heme-binding glutathione S-transferases from the human hookworm Necator americanus. Infection and Immunity 78, 1552–1563.10.1128/IAI.00848-09CrossRefGoogle ScholarPubMed
Zhan, B, Beaumier, CM, Briggs, N, Jones, KM, Keegan, BP, Bottazzi, ME and Hotez, PJ (2014) Advancing a multivalent ‘Pan-anthelmintic’ vaccine against soil-transmitted nematode infections. Expert Review of Vaccines 13, 321–331.10.1586/14760584.2014.872035CrossRefGoogle ScholarPubMed