Hostname: page-component-848d4c4894-p2v8j Total loading time: 0 Render date: 2024-04-30T10:15:19.228Z Has data issue: false hasContentIssue false
  • English
  • Français

The excretory–secretory antigen HcADRM1 to generate protective immunity against Haemonchus contortus

Published online by Cambridge University Press:  30 June 2021

Mingmin Lu Open the ORCID record for Mingmin Lu [Opens in a new window] ,
Xiaowei Tian ,
Wenjuan Wang ,
Yang Zhang ,
Kalibixiati Aimulajiang ,
Ai-Ling Tian ,
Charles Li ,
Ruofeng Yan Open the ORCID record for Ruofeng Yan [Opens in a new window] ,
Lixin Xu  and
Xiaokai Song
...Show all authors
Mingmin Lu
Affiliation:
MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu 210095, P. R. China
Xiaowei Tian
Affiliation:
MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu 210095, P. R. China
Wenjuan Wang
Affiliation:
MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu 210095, P. R. China
Yang Zhang
Affiliation:
MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu 210095, P. R. China
Kalibixiati Aimulajiang
Affiliation:
MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu 210095, P. R. China
Ai-Ling Tian
Affiliation:
State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province 730046, P. R. China
Charles Li
Affiliation:
U.S. Department of Agriculture, Animal Biosciences and Biotechnology Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, Beltsville, MD 20705, USA
Ruofeng Yan
Affiliation:
MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu 210095, P. R. China
Lixin Xu
Affiliation:
MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu 210095, P. R. China
Xiaokai Song
Affiliation:
MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu 210095, P. R. China
Xiangrui Li*
Affiliation:
MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu 210095, P. R. China
*
Author for correspondence: Xiangrui Li, E-mail: lixiangrui@njau.edu.cn
Get access Rights & Permissions [Opens in a new window]

Abstract

The prevention, treatment and control of Haemonchus contortus have been increasingly problematic due to its widespread occurrence and anthelmintic resistance. There are very few descriptions of recombinant antigens being protective for H. contortus, despite the success of various native antigen preparations, including Barbervax. We recently identified an H. contortus excretory–secretory antigen, H. contortus adhesion-regulating molecule 1 (HcADRM1), that served as an immunomodulator to impair host T-cell functions. Given the prophylactic potential of HcADRM1 protein as a vaccine candidate, we hereby assessed the efficacies of HcADRM1 preparations against H. contortus infection. Parasitological and immunological parameters were evaluated throughout all time points of the trials, including fecal egg counts (FEC), abomasal worm burdens, complete blood counts, cytokine production profiles and antibody responses. Active vaccination with recombinant HcADRM1 (rHcADRM1) protein induced protective immunity in inoculated goats, resulting in reductions of 48.9 and 58.6% in cumulative FEC and worm burdens. Simultaneously, passive administration of anti-HcADRM1 antibodies generated encouraging levels of protection with 46.7 and 56.2% reductions in cumulative FEC and worm burdens in challenged goats. In addition, HcADRM1 preparations-immunized goats showed significant differences in mucosal and serum antigen-specific immunoglobulin G (IgG) levels, total mucosal IgA levels, haemoglobin values and circulating interferon-γ, interleukin (IL)-4 and IL-17A production compared to control goats in both trials. The preliminary data of these laboratory trials validated the immunoprophylactic effects of rHcADRM1 protein. It can be pursued as a potential vaccine antigen to develop an effective recombinant subunit vaccine against H. contortus under field conditions.

Keywords

Adhesion-regulating molecule 1goatH. contortusimmunizationprotective immunity
Type
Research Article
Information
Parasitology , Volume 148 , Issue 12 , October 2021 , pp. 1497 - 1508
Check for updates
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Bakker, N, Vervelde, L, Kanobana, K, Knox, D, Cornelissen, A, De Vries, E and Yatsuda, A (2004) Vaccination against the nematode Haemonchus contortus with a thiol-binding fraction from the excretory/secretory products (ES). Vaccine 22, 618–628.CrossRefGoogle ScholarPubMed
Balic, A, Bowles, V and Meeusen, ENT (2002) Mechanisms of immunity to Haemonchus contortus infection in sheep. Parasite Immunology 24, 39–46.CrossRefGoogle ScholarPubMed
Balic, A, Cunningham, C and Meeusen, ENT (2006) Eosinophil interactions with Haemonchus contortus larvae in the ovine gastrointestinal tract. Parasite Immunology 28, 107–115.CrossRefGoogle ScholarPubMed
Bassetto, C, Silva, B, Newlands, G, Smith, W and Amarante, AD (2011) Protection of calves against Haemonchus placei and Haemonchus contortus after immunization with gut membrane proteins from H. contortus. Parasite Immunology 33, 377–381.CrossRefGoogle ScholarPubMed
Besier, R, Kahn, L, Sargison, N and Van Wyk, J (2016a) Diagnosis, treatment and management of Haemonchus contortus in small ruminants. Advances in Parasitology 93, 181–238.CrossRefGoogle ScholarPubMed
Besier, R, Kahn, L, Sargison, N and Van Wyk, J (2016b) The pathophysiology, ecology and epidemiology of Haemonchus contortus infection in small ruminants. Advances in Parasitology 93, 95–143.CrossRefGoogle ScholarPubMed
Bethony, JM, Cole, RN, Guo, X, Kamhawi, S, Lightowlers, MW, Loukas, A, Petri, W, Reed, S, Valenzuela, JG and Hotez, PJ (2011) Vaccines to combat the neglected tropical diseases. Immunological Reviews 239, 237–270.CrossRefGoogle ScholarPubMed
Britton, C, Emery, DL, McNeilly, TN, Nisbet, AJ and Stear, MJ (2020) The potential for vaccines against scour worms of small ruminants. International Journal for Parasitology 50, 533–553.CrossRefGoogle ScholarPubMed
Bu, Y, Jia, C, Tian, X, Aimulajiang, K, Memon, MA, Yan, R, Song, X, Xu, L and Li, X (2020) Immunization of goats with recombinant protein 14-3-3 isoform 2 (rHcftt-2) induced moderate protection against Haemonchus contortus challenge. Pathogens (Basel, Switzerland) 9, 46.Google ScholarPubMed
Cachat, E, Newlands, G, Ekoja, S, McAllister, H and Smith, W (2010) Attempts to immunize sheep against Haemonchus contortus using a cocktail of recombinant proteases derived from the protective antigen, H-gal-GP. Parasite Immunology 32, 414–419.CrossRefGoogle ScholarPubMed
Chen, F, Liu, Z, Wu, W, Rozo, C, Bowdridge, S, Millman, A, Van Rooijen, N, Urban, JF, Wynn, TA and Gause, WC (2012) An essential role for TH 2-type responses in limiting acute tissue damage during experimental helminth infection. Nature Medicine 18, 260–266.CrossRefGoogle Scholar
Cortés, A, Muñoz-Antoli, C, Esteban, JG and Toledo, R (2017) Th2 and Th1 responses: clear and hidden sides of immunity against intestinal helminths. Trends in Parasitology 33, 678–693.CrossRefGoogle ScholarPubMed
De Vries, E, Bakker, N, Krijgsveld, J, Knox, DP, Heck, AJ and Yatsuda, AP (2009) An AC-5 cathepsin B-like protease purified from Haemonchus contortus excretory secretory products shows protective antigen potential for lambs. Veterinary Research 40, 1–11.CrossRefGoogle ScholarPubMed
Ehsan, M, Gao, W, Gadahi, JA, Lu, M, Liu, X, Wang, Y, Yan, R, Xu, L, Song, X and Li, X (2017) Arginine kinase from Haemonchus contortus decreased the proliferation and increased the apoptosis of goat PBMCs in vitro. Parasites & Vectors 10, 311.CrossRefGoogle ScholarPubMed
Ehsan, M, Wang, W, Gadahi, JA, Hasan, MW, Lu, M, Wang, Y, Liu, X, Haseeb, M, Yan, R and Xu, L (2018) The serine/threonine-protein phosphatase 1 from Haemonchus contortus is actively involved in suppressive regulatory roles on immune functions of goat peripheral blood mononuclear cells. Frontiers in Immunology 9, 1627.CrossRefGoogle ScholarPubMed
Emery, DL, Hunt, PW and Le Jambre, LF (2016) Haemonchus contortus: the then and now, and where to from here? International Journal for Parasitology 46, 755–769.CrossRefGoogle Scholar
Fawzi, EM, González-Sánchez, ME, Corral, MJ, Alunda, JM and Cuquerella, M (2015) Vaccination of lambs with the recombinant protein rHc23 elicits significant protection against Haemonchus contortus challenge. Veterinary Parasitology 211, 54–59.CrossRefGoogle ScholarPubMed
Foreyt, WJ (2013) Veterinary Parasitology Reference Manual. New York, USA: John Wiley & Sons.Google Scholar
Gonçalves-de-Albuquerque, SDC, Pessoa-e-Silva, R, Trajano-Silva, LA, de Goes, TC, de Morais, R, da Oliveira, CNC, de Lorena, V and de Paiva-Cavalcanti, M (2017) The equivocal role of Th17 cells and neutrophils on immunopathogenesis of leishmaniasis. Frontiers in Immunology 8, 1437.CrossRefGoogle ScholarPubMed
Grencis, RK, Humphreys, NE and Bancroft, AJ (2014) Immunity to gastrointestinal nematodes: mechanisms and myths. Immunological Reviews 260, 183–205.CrossRefGoogle ScholarPubMed
Harnett, W (2014) Secretory products of helminth parasites as immunomodulators. Molecular and Biochemical Parasitology 195, 130–136.CrossRefGoogle ScholarPubMed
Harris, NL (2017) Recent advances in type-2-cell-mediated immunity: insights from helminth infection. Immunity 47, 1024–1036.CrossRefGoogle ScholarPubMed
HogenEsch, H (2013) Mechanism of immunopotentiation and safety of aluminum adjuvants. Frontiers in Immunology 3, 406.CrossRefGoogle ScholarPubMed
Husnjak, K, Elsasser, S, Zhang, N, Chen, X, Randles, L, Shi, Y, Hofmann, K, Walters, KJ, Finley, D and Dikic, I (2008) Proteasome subunit Rpn13 is a novel ubiquitin receptor. Nature 453, 481–488.CrossRefGoogle ScholarPubMed
Jasmer, D, Perryman, L, Conder, G, Crow, S and McGuire, T (1993) Protective immunity to Haemonchus contortus induced by immunoaffinity isolated antigens that share a phylogenetically conserved carbohydrate gut surface epitope. The Journal of Immunology 151, 5450–5460.CrossRefGoogle Scholar
Kalyanasundaram, A, Jawahar, S, Ilangopathy, M, Palavesam, A and Raman, M (2015) Comparative immunoprophylactic efficacy of Haemonchus contortus recombinant enolase (rHcENO) and Con A purified native glycoproteins in sheep. Experimental Parasitology 154, 98–107.CrossRefGoogle ScholarPubMed
Kearney, P, Murray, P, Hoy, J, Hohenhaus, M and Kotze, A (2016) The ‘Toolbox’ of strategies for managing Haemonchus contortus in goats: what's in and what's out. Veterinary Parasitology 220, 93–107.CrossRefGoogle ScholarPubMed
Kemp, JM, Robinson, NA, Meeusen, EN and Piedrafita, DM (2009) The relationship between the rapid rejection of Haemonchus contortus larvae with cells and mediators in abomasal tissues in immune sheep. International Journal for Parasitology 39, 1589–1594.CrossRefGoogle ScholarPubMed
Kotze, A and Prichard, R (2016) Anthelmintic resistance in Haemonchus contortus: history, mechanisms and diagnosis. Advances in Parasitology 93, 397–428.CrossRefGoogle ScholarPubMed
Lacroux, C, Nguyen, THC, Andreoletti, O, Prevot, F, Grisez, C, Bergeaud, J-P, Gruner, L, Brunel, J-C, Francois, D and Dorchies, P (2006) Haemonchus contortus (Nematoda: Trichostrongylidae) infection in lambs elicits an unequivocal Th2 immune response. Veterinary Research 37, 607–622.CrossRefGoogle ScholarPubMed
LeJambre, L, Windon, R and Smith, W (2008) Vaccination against Haemonchus contortus: performance of native parasite gut membrane glycoproteins in Merino lambs grazing contaminated pasture. Veterinary Parasitology 153, 302–312.CrossRefGoogle ScholarPubMed
Lu, M, Tian, X, Tian, A-L, Li, C, Yan, R, Xu, L, Song, X and Li, X (2020a) A novel α/β hydrolase domain protein derived from Haemonchus Contortus acts at the parasite-host interface. Frontiers in Immunology 11, 1388.CrossRefGoogle ScholarPubMed
Lu, M, Tian, X, Yang, Z, Wang, W, Tian, A-L, Li, C, Yan, R, Xu, L, Song, X and Li, X (2020b) Proteomic analysis revealed T cell hyporesponsiveness induced by Haemonchus contortus excretory and secretory proteins. Veterinary Research 51, 1–14.CrossRefGoogle ScholarPubMed
Lu, M, Tian, X, Zhang, Y, Aimulajiang, K, Wang, W, Ehsan, M, Li, C, Yan, R, Xu, L and Song, X (2020c) Unveiling the immunomodulatory properties of Haemonchus contortus adhesion regulating molecule 1 interacting with goat T cells. Parasites & Vectors 13, 1–13.CrossRefGoogle ScholarPubMed
Matthews, J, Geldhof, P, Tzelos, T and Claerebout, E (2016) Progress in the development of subunit vaccines for gastrointestinal nematodes of ruminants. Parasite Immunology 38, 744–753.CrossRefGoogle ScholarPubMed
McSorley, HJ, Hewitson, JP and Maizels, RM (2013) Immunomodulation by helminth parasites: defining mechanisms and mediators. International Journal for Parasitology 43, 301–310.CrossRefGoogle ScholarPubMed
Murray, L, Geldhof, P, Clark, D, Knox, DP and Britton, C (2007) Expression and purification of an active cysteine protease of Haemonchus contortus using Caenorhabditis elegans. International Journal for Parasitology 37, 1117–1125.CrossRefGoogle ScholarPubMed
Newton, SA and Munn, E (1999) The development of vaccines against gastrointestinal nematode parasites, particularly Haemonchus contortus. Parasitology Today 15, 116–122.CrossRefGoogle ScholarPubMed
Nisbet, AJ, McNeilly, TN, Wildblood, LA, Morrison, AA, Bartley, DJ, Bartley, Y, Longhi, C, McKendrick, IJ, Palarea-Albaladejo, J and Matthews, JB (2013) Successful immunization against a parasitic nematode by vaccination with recombinant proteins. Vaccine 31, 4017–4023.CrossRefGoogle ScholarPubMed
Nisbet, A, Meeusen, E, González, J and Piedrafita, D (2016) Immunity to Haemonchus contortus and vaccine development. Advances in Parasitology 93, 353–396.CrossRefGoogle ScholarPubMed
Noon, JB and Aroian, RV (2017) Recombinant subunit vaccines for soil-transmitted helminths. Parasitology 144, 1845–1870.CrossRefGoogle ScholarPubMed
Petrovsky, N (2015) Comparative safety of vaccine adjuvants: a summary of current evidence and future needs. Drug Safety 38, 1059–1074.CrossRefGoogle ScholarPubMed
Piedrafita, D, de Veer, MJ, Sherrard, J, Kraska, T, Elhay, M and Meeusen, EN (2012) Field vaccination of sheep with a larval-specific antigen of the gastrointestinal nematode, Haemonchus contortus, confers significant protection against an experimental challenge infection. Vaccine 30, 7199–7204.CrossRefGoogle ScholarPubMed
Reed, SG, Orr, MT and Fox, CB (2013) Key roles of adjuvants in modern vaccines. Nature Medicine 19, 1597–1608.CrossRefGoogle ScholarPubMed
Reszka, N, Rijsewijk, FA, Zelnik, V, Moskwa, B and Bieńkowska-Szewczyk, K (2007) Haemonchus contortus: characterization of the baculovirus expressed form of aminopeptidase H11. Experimental Parasitology 117, 208–213.CrossRefGoogle ScholarPubMed
Roberts, B, Antonopoulos, A, Haslam, SM, Dicker, AJ, McNeilly, TN, Johnston, SL, Dell, A, Knox, DP and Britton, C (2013) Novel expression of Haemonchus contortus vaccine candidate aminopeptidase H11 using the free-living nematode Caenorhabditis elegans. Veterinary Research 44, 111.CrossRefGoogle ScholarPubMed
Robinson, N, Piedrafita, D, Snibson, K, Harrison, P and Meeusen, EN (2010) Immune cell kinetics in the ovine abomasal mucosa following hyperimmunization and challenge with Haemonchus contortus. Veterinary Research 41, 37.CrossRefGoogle ScholarPubMed
Schallig, HD, Van Leeuwen, MA and Cornelissen, AW (1997) Protective immunity induced by vaccination with two Haemonchus contortus excretory secretory proteins in sheep. Parasite Immunology 19, 447–453.CrossRefGoogle ScholarPubMed
Smith, W, Newlands, G, Smith, S, Pettit, D and Skuce, P (2003) Metalloendopeptidases from the intestinal brush border of Haemonchus contortus as protective antigens for sheep. Parasite Immunology 25, 313–323.CrossRefGoogle ScholarPubMed
Sorobetea, D, Svensson-Frej, M and Grencis, R (2018) Immunity to gastrointestinal nematode infections. Mucosal Immunology 11, 304–315.CrossRefGoogle ScholarPubMed
Stear, M, Bairden, K, Innocent, G, Mitchell, S, Strain, S and Bishop, S (2004) The relationship between IgA activity against 4th-stage larvae and density-dependent effects on the number of 4th-stage larvae of Teladorsagia circumcincta in naturally infected sheep. Parasitology 129, 363.CrossRefGoogle ScholarPubMed
Taylor, S, Kenny, J, Edgar, H, Ellison, S and Ferguson, L (1997) Efficacy of moxidectin, ivermectin and albendazole oral drenches for suppression of periparturient rise in ewe worm egg output and reduction of anthelmintic treatment for lambs. Veterinary Record 141, 357–360.CrossRefGoogle ScholarPubMed
Tian, X, Lu, M, Wang, W, Jia, C, Muhammad, E, Yan, R, Xu, L, Song, X and Li, X (2019) Hc TTR: a novel antagonist against goat interleukin 4 derived from the excretory and secretory products of Haemonchus contortus. Veterinary Research 50, 1–11.CrossRefGoogle Scholar
Tian, X, Lu, M, Jia, C, Bu, Y, Aimulajiang, K, Zhang, Y, Li, C, Yan, R, Xu, L and Song, X (2020) Haemonchus contortus transthyretin domain-containing protein (HcTTR): a promising vaccine candidate against Haemonchus contortus infection. Veterinary Parasitology 279, 109045.CrossRefGoogle ScholarPubMed
VanHoy, G, Carman, M, Habing, G, Lakritz, J, Hinds, CA, Niehaus, A, Kaplan, RM and Marsh, AE (2018) Safety and serologic response to a Haemonchus contortus vaccine in alpacas. Veterinary Parasitology 252, 180–186.CrossRefGoogle ScholarPubMed
van Stijn, CM, van den Broek, M, Vervelde, L, Alvarez, RA, Cummings, RD, Tefsen, B and van Die, I (2010) Vaccination-induced IgG response to Galα1–3GalNAc glycan epitopes in lambs protected against Haemonchus contortus challenge infection. International Journal for Parasitology 40, 215–222.CrossRefGoogle ScholarPubMed
Wang, W, Wang, S, Zhang, H, Yuan, C, Yan, R, Song, X, Xu, L and Li, X (2014) Galectin Hco-gal-m from Haemonchus contortus modulates goat monocytes and T cell function in different patterns. Parasites & Vectors 7, 1–12.CrossRefGoogle Scholar
Wang, F, Xu, L, Song, X, Li, X and Yan, R (2016) Identification of differentially expressed proteins between free-living and activated third-stage larvae of Haemonchus contortus. Veterinary Parasitology 215, 72–77.CrossRefGoogle ScholarPubMed
Wang, Q, Wu, L, Hasan, MW, Lu, M, Wang, W, Yan, R, Xu, L, Song, X and Li, X (2019a) Hepatocellular carcinoma-associated antigen 59 of Haemonchus contortus modulates the functions of PBMCs and the differentiation and maturation of monocyte-derived dendritic cells of goats in vitro. Parasites & Vectors 12, 1–14.CrossRefGoogle ScholarPubMed
Wang, W, Wang, Y, Tian, X, Lu, M, Ehsan, M, Yan, R, Song, X, Xu, L and Li, X (2019b) Y75B8A.8 (HC8) protein of Haemonchus contortus: a functional inhibitor of host IL-2. Parasite Immunology 41, e12625.CrossRefGoogle ScholarPubMed
Wen, Y, Wang, Y, Wang, W, Lu, M, Ehsan, M, Tian, X, Yan, R, Song, X, Xu, L and Li, X (2017) Recombinant Miro domain-containing protein of Haemonchus contortus (rMiro-1) activates goat peripheral blood mononuclear cells in vitro. Veterinary Parasitology 243, 100–104.CrossRefGoogle ScholarPubMed
Yanming, S, Ruofeng, Y, Muleke, C, Guangwei, Z, Lixin, X and Xiangrui, L (2007) Vaccination of goats with recombinant galectin antigen induces partial protection against Haemonchus contortus infection. Parasite Immunology 29, 319–326.CrossRefGoogle ScholarPubMed
Yazdanbakhsh, M, Kremsner, PG and Van Ree, R (2002) Allergy, parasites, and the hygiene hypothesis. Science (New York, N.Y.) 296, 490–494.CrossRefGoogle ScholarPubMed
Zaros, L, Neves, M, Benvenuti, C, Navarro, A, Sider, L, Coutinho, L and Vieira, L (2014) Response of resistant and susceptible Brazilian Somalis crossbreed sheep naturally infected by Haemonchus contortus. Parasitology research 113, 1155–1161.CrossRefGoogle ScholarPubMed
Zhang, Z, Liu, L, Huang, J, Wang, S, Lu, M, Song, X, Xu, L, Yan, R and Li, X (2016) The molecular characterization and immune protection of microneme 2 of Eimeria acervulina. Veterinary Parasitology 215, 96–105.CrossRefGoogle ScholarPubMed
Supplementary material: File

Lu et al. supplementary material

Lu et al. supplementary material

Download Lu et al. supplementary material(File)
File 12 MB