A Two-Component DNA-Prime/Protein-Boost Vaccination Strategy for Eliciting Long-Term, Protective T Cell Immunity against

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Chagas disease, caused by Trypanosoma cruzi infection, represents the third greatest tropical disease burden in the world. No vaccine or suitable treatment is available for control of this infection. Based upon several studies we have conducted, we believe that TcG2 and TcG4 candidate antigens that are highly conserved in T. cruzi, expressed in clinically relevant forms of the parasite, and recognized by both B and T cell responses in multiple hosts, are an excellent choice for subunit vaccine development. In this study, we demonstrate that the delivery of TcG2 and TcG4 as a DNA-prime/protein-boost vaccine provided long-term protection from challenge infection, and this protection was associated with elicitation of long-lived CD8+ effector T cells. The longevity and efficacy of vaccine could be enhanced by booster immunization. We believe that this is the first report demonstrating a) a subunit vaccine can be useful in achieving long-term protection against T. cruzi infection and Chagas disease, and b) the effector T cells can be long-lived and play a role in vaccine elicited protection from parasitic infection.

Vyšlo v časopise: A Two-Component DNA-Prime/Protein-Boost Vaccination Strategy for Eliciting Long-Term, Protective T Cell Immunity against. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004828
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004828

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Zdroje

1. World Health Organization (2010) Chagas disease: control and elimination. UNDP/World Bank/WHO. http://apps.who.int/gb/ebwha/pdf_files/WHA63/A63_17-en.pdf, accessed on Mar 5, 2015.

2. Cunha-Neto E, Chevillard C (2014) Chagas disease cardiomyopathy: immunopathology and genetics. Mediators Inflamm 2014 : 683230. doi: 10.1155/2014/683230 25210230

3. Cantey PT, Stramer SL, Townsend RL, Kamel H, Ofafa K, et al. (2012) The United States Trypanosoma cruzi Infection Study: evidence for vector-borne transmission of the parasite that causes Chagas disease among United States blood donors. Transfusion.

4. Bern C, Kjos S, Yabsley MJ, Montgomery SP (2011) Trypanosoma cruzi and Chagas' Disease in the United States. Clin Microbiol Rev 24 : 655–681. doi: 10.1128/CMR.00005-11 21976603

5. Bern C, Montgomery SP (2009) An estimate of the burden of Chagas disease in the United States. Clin Infect Dis 49: e52–54. doi: 10.1086/605091 19640226

6. Tanowitz HB, Weiss LM, Montgomery SP (2011) Chagas disease has now gone global. PLoS Negl Trop Dis 5: e1136. doi: 10.1371/journal.pntd.0001136 21572510

7. Vázquez-Chagoyán JC, Gupta S, Garg NJ (2011) Vaccine development against Trypanosoma cruzi and Chagas disease. Advanced parasitol 75 : 121–146. doi: 10.1016/B978-0-12-385863-4.00006-X 21820554

8. Lee BY, Bacon KM, Connor DL, Willig AM, Bailey RR (2010) The potential economic value of a Trypanosoma cruzi (Chagas disease) vaccine in Latin America. PLoS Negl Trop Dis 4: e916. doi: 10.1371/journal.pntd.0000916 21179503

9. Garg NJ, Tarleton RL (2002) Genetic immunization elicits antigen-specific protective immune responses and decreases disease severity in Trypanosoma cruzi infection. Infection & Immunity 70 : 5547–5555.

10. Bhatia V, Sinha M, Luxon B, Garg NJ (2004) Utility of Trypanosoma cruzi sequence database for the identification of potential vaccine candidates: In silico and in vitro screening. Infect Immun 72 : 6245–6254. 15501750

11. Bhatia V, Garg NJ (2008) Previously unrecognized vaccine candidates control Trypanosoma cruzi infection and immunopathology in mice. Clin Vaccine Immunol 15 : 1158–1164. doi: 10.1128/CVI.00144-08 18550728

12. Aparicio-Burgos JE, Ochoa-Garcia L, Zepeda-Escobar JA, Gupta S, Dhiman M, et al. (2011) Testing the efficacy of a multi-component DNA-prime/DNA-boost vaccine against Trypanosoma cruzi infection in dogs. PLoS Negl Trop Dis 5: e1050. doi: 10.1371/journal.pntd.0001050 21625470

13. Gupta S, Garg NJ (2010) Prophylactic efficacy of TcVac2 against Trypanosoma cruzi in mice. PLoS Negl Trop Dis 4: e797. doi: 10.1371/journal.pntd.0000797 20706586

14. Tanowitz HB, Machado FS, Jelicks LA, Shirani J, de Carvalho AC, et al. (2009) Perspectives on Trypanosoma cruzi-induced heart disease (Chagas disease). Prog Cardiovasc Dis 51 : 524–539. doi: 10.1016/j.pcad.2009.02.001 19410685

15. Ribeiro AL, Nunes MP, Teixeira MM, Rocha MO (2012) Diagnosis and management of Chagas disease and cardiomyopathy. Nat Rev Cardiol 9 : 576–589. doi: 10.1038/nrcardio.2012.109 22847166

16. Machado FS, Tyler KM, Brant F, Esper L, Teixeira MM, et al. (2012) Pathogenesis of Chagas disease: time to move on. Front Biosci (Elite Ed) 4 : 1743–1758. 22201990

17. Machado FS, Dutra WO, Esper L, Gollob KJ, Teixeira MM, et al. (2012) Current understanding of immunity to Trypanosoma cruzi infection and pathogenesis of Chagas disease. Seminars in Immunopathology 34 : 753–770. doi: 10.1007/s00281-012-0351-7 23076807

18. Tarleton RL (2007) Immune system recognition of Trypanosoma cruzi. Curr Opin Immunol 19 : 430–434. 17651955

19. Padilla AM, Bustamante JM, Tarleton RL (2009) CD8+ T cells in Trypanosoma cruzi infection. Curr Opin Immunol 21 : 385–390. doi: 10.1016/j.coi.2009.07.006 19646853

20. Bhatia V, Garg NJ (2005) Current status and future prospects for a vaccine against American trypanosomiasis. Expert Rev Vaccines 4 : 867–880. 16372882

21. Bhatia V, Wen J-J, Zacks MA, Garg NJ (2009) American trypanosomiasis and perspectives on vaccine development. In: Stanberry LR, Barrett AD, editors. Vaccines for Biodefense and Emerging and Neglected Diseases. New York: Academic Press. pp. 1407–1434.

22. Vazquez-Chagoyan JC, Gupta S, Garg NJ (2011) Vaccine development against Trypanosoma cruzi and Chagas disease. Adv Parasitol 75 : 121–146. doi: 10.1016/B978-0-12-385863-4.00006-X 21820554

23. Cazorla SI, Becker PD, Frank FM, Ebensen T, Sartori MJ, et al. (2008) Oral vaccination with Salmonella enterica as a cruzipain-DNA delivery system confers protective immunity against Trypanosoma cruzi. Infect Immun 76 : 324–333. 17967857

24. Miyahira Y, Takashima Y, Kobayashi S, Matsumoto Y, Takeuchi T, et al. (2005) Immune responses against a single CD8+-T-cell epitope induced by virus vector vaccination can successfully control Trypanosoma cruzi infection. Infect Immun 73 : 7356–7365. 16239534

25. de Alencar BC, Persechini PM, Haolla FA, de Oliveira G, Silverio JC, et al. (2009) Perforin and gamma interferon expression are required for CD4+ and CD8+ T-cell-dependent protective immunity against a human parasite, Trypanosoma cruzi, elicited by heterologous plasmid DNA prime-recombinant adenovirus 5 boost vaccination. Infect Immun 77 : 4383–4395. doi: 10.1128/IAI.01459-08 19651871

26. Gupta S, Wan X-X, Zago MP, Martinez VCS, Silva TS, et al. (2013) Antigenicity and diagnostic potential of vaccine candidates in human Chagas disease,. Plos NTD 7: e2018. doi: 10.1371/journal.pntd.0002018 23350012

27. Gupta S, Garg NJ (2012) Delivery of antigenic candidates by a DNA/MVA heterologous approach elicits effector CD8+T cell mediated immunity against Trypanosoma cruzi. Vaccine 12 : 1464–1478

28. Gupta S, Garg NJ (2013) TcVac3 induced control of Trypanosoma cruzi infection and chronic myocarditis in mice. PLOS ONE 8: e59434. doi: 10.1371/journal.pone.0059434 23555672

29. Huygen K (2005) Plasmid DNA vaccination. Microbes Infect 7 : 932–938. 15878683

30. Donnelly JJ, Wahren B, Liu MA (2005) DNA vaccines: progress and challenges. J Immunol 175 : 633–639. 16002657

31. Scharpe J, Peetermans WE, Vanwalleghem J, Maes B, Bammens B, et al. (2009) Immunogenicity of a standard trivalent influenza vaccine in patients on long-term hemodialysis: an open-label trial. Am J Kidney Dis 54 : 77–85. doi: 10.1053/j.ajkd.2008.11.032 19339089

32. Zeng R, Zhang Z, Mei X, Gong W, Wei L (2008) Protective effect of a RSV subunit vaccine candidate G1F/M2 was enhanced by a HSP70-Like protein in mice. Biochem Biophys Res Commun 377 : 495–499. doi: 10.1016/j.bbrc.2008.10.002 18851947

33. Limon-Flores AY, Cervera-Cetina R, Tzec-Arjona JL, Ek-Macias L, Sanchez-Burgos G, et al. (2010) Effect of a combination DNA vaccine for the prevention and therapy of Trypanosoma cruzi infection in mice: role of CD4+ and CD8+ T cells. Vaccine 28 : 7414–7419. doi: 10.1016/j.vaccine.2010.08.104 20850536

34. Dutra WO, Gollob KJ (2008) Current concepts in immunoregulation and pathology of human Chagas disease. Curr Opin Infect Dis 21 : 287–292. doi: 10.1097/QCO.0b013e3282f88b80 18448974

35. Gomes JA, Bahia-Oliveira LM, Rocha MO, Martins-Filho OA, Gazzinelli G, et al. (2003) Evidence that development of severe cardiomyopathy in human Chagas' disease is due to a Th1-specific immune response. Infect Immun 71 : 1185–1193. 12595431

36. Laucella SA, Postan M, Martin D, Hubby Fralish B, Albareda MC, et al. (2004) Frequency of interferon -⁠ gamma-producing T cells specific for Trypanosoma cruzi inversely correlates with disease severity in chronic human Chagas disease. J Infect Dis 189 : 909–918. 14976609

37. Gomes JA, Bahia-Oliveira LM, Rocha MO, Busek SC, Teixeira MM, et al. (2005) Type 1 chemokine receptor expression in Chagas' disease correlates with morbidity in cardiac patients. Infect Immun 73 : 7960–7966. 16299288

38. Magalhaes LM, Villani FN, Nunes Mdo C, Gollob KJ, Rocha MO, et al. (2013) High interleukin 17 expression is correlated with better cardiac function in human Chagas disease. J Infect Dis 207 : 661–665. doi: 10.1093/infdis/jis724 23204182

39. Silva GK, Gutierrez FR, Guedes PM, Horta CV, Cunha LD, et al. (2010) Cutting edge: nucleotide-binding oligomerization domain 1-dependent responses account for murine resistance against Trypanosoma cruzi infection. J Immunol 184 : 1148–1152. doi: 10.4049/jimmunol.0902254 20042586

40. Rodrigues MM, Oliveira AC, Bellio M (2012) The Immune Response to Trypanosoma cruzi: Role of Toll-Like Receptors and Perspectives for Vaccine Development. J Parasitol Res 2012 : 507874. doi: 10.1155/2012/507874 22496959

41. Goncalves VM, Matteucci KC, Buzzo CL, Miollo BH, Ferrante D, et al. (2013) NLRP3 controls Trypanosoma cruzi infection through a caspase-1-dependent IL-1R-independent NO production. PLoS Negl Trop Dis 7: e2469. doi: 10.1371/journal.pntd.0002469 24098823

42. Tarleton RL, Grusby MJ, Postan M, Glimcher LH (1996) Trypanosoma cruzi infection in MHC-deficient mice: further evidence for the role of both class I -⁠ and class II-restricted T cells in immune resistance and disease. Int Immunol 8 : 13–22. 8671585

43. Nickell SP, Sharma D (2000) Trypanosoma cruzi: roles for perforin-dependent and perforin-independent immune mechanisms in acute resistance. Exp Parasitol 94 : 207–216. 10831388

44. Tzelepis F, de Alencar BC, Penido ML, Gazzinelli RT, Persechini PM, et al. (2006) Distinct kinetics of effector CD8+ cytotoxic T cells after infection with Trypanosoma cruzi in naive or vaccinated mice. Infect Immun 74 : 2477–2481. 16552083

45. Masopust D, Ahmed R (2004) Reflections on CD8 T-cell activation and memory. Immunol Res 29 : 151–160. 15181278

46. Tzelepis F, de Alencar BC, Penido ML, Claser C, Machado AV, et al. (2008) Infection with Trypanosoma cruzi restricts the repertoire of parasite-specific CD8+ T cells leading to immunodominance. J Immunol 180 : 1737–1748. 18209071

47. Eickhoff CS, Vasconcelos JR, Sullivan NL, Blazevic A, Bruna-Romero O, et al. (2011) Co-administration of a plasmid DNA encoding IL-15 improves long-term protection of a genetic vaccine against Trypanosoma cruzi. PLoS Negl Trop Dis 5: e983. doi: 10.1371/journal.pntd.0000983 21408124

48. Vasconcelos JR, Bruna-Romero O, Araujo AF, Dominguez MR, Ersching J, et al. (2012) Pathogen-induced proapoptotic phenotype and high CD95 (Fas) expression accompany a suboptimal CD8+ T-cell response: reversal by adenoviral vaccine. PLoS Pathog 8: e1002699. doi: 10.1371/journal.ppat.1002699 22615561

49. Vezys V, Yates A, Casey KA, Lanier G, Ahmed R, et al. (2009) Memory CD8 T-cell compartment grows in size with immunological experience. Nature 457 : 196–199. doi: 10.1038/nature07486 19005468

50. DiSpirito JR, Shen H (2010) Quick to remember, slow to forget: rapid recall responses of memory CD8+ T cells. Cell Res 20 : 13–23. doi: 10.1038/cr.2009.140 20029390

51. Zanetti M, Castiglioni P, Ingulli E (2010) Principles of memory CD8 T-cells generation in relation to protective immunity. Adv Exp Med Biol 684 : 108–125. 20795544

52. Peters NC, Pagan AJ, Lawyer PG, Hand TW, Henrique Roma E, et al. (2014) Chronic parasitic infection maintains high frequencies of short-lived Ly6C+CD4+ effector T cells that are required for protection against re-infection. PLoS Pathog 10: e1004538. doi: 10.1371/journal.ppat.1004538 25473946

53. Rigato PO, de Alencar BC, de Vasconcelos JR, Dominguez MR, Araujo AF, et al. (2011) Heterologous plasmid DNA prime-recombinant human adenovirus 5 boost vaccination generates a stable pool of protective long-lived CD8(+) T effector memory cells specific for a human parasite, Trypanosoma cruzi. Infect Immun 79 : 2120–2130. doi: 10.1128/IAI.01190-10 21357719

54. Albareda MC, Laucella SA, Alvarez MG, Armenti AH, Bertochi G, et al. (2006) Trypanosoma cruzi modulates the profile of memory CD8+ T cells in chronic Chagas' disease patients. Int Immunol 18 : 465–471. 16431876

55. Bustamante JM, Bixby LM, Tarleton RL (2008) Drug-induced cure drives conversion to a stable and protective CD8+ T central memory response in chronic Chagas disease. Nat Med 14 : 542–550. doi: 10.1038/nm1744 18425131

56. Dos Santos Virgilio F, Pontes C, Dominguez MR, Ersching J, Rodrigues MM, et al. (2014) CD8(+) T cell-mediated immunity during Trypanosoma cruzi infection: a path for vaccine development? Mediators Inflamm 2014 : 243786. doi: 10.1155/2014/243786 25104879

57. Cohen JE, Gurtler RE (2001) Modeling household transmission of American trypanosomiasis. Science 293 : 694–698. 11474111

58. Earl PL MB, Wyatt LS, Carroll MW. (1998) Generation of recombinant vaccinia viruses. In: Current Protocols in Molecular Biology. Ausubel FM, Brent R, Kingston RE, Moore DD, Seidmen ZG, Smith ZA, Skuhl LX (eds). John Wiley and Sons: NewYork, pp 16.17.11–16.19.11.

59. Sandstrom E, Nilsson C, Hejdeman B, Brave A, Bratt G, et al. (2008) Broad immunogenicity of a multigene, multiclade HIV-1 DNA vaccine boosted with heterologous HIV-1 recombinant modified vaccinia virus Ankara. J Infect Dis 198 : 1482–1490. doi: 10.1086/592507 18808335

60. Garg NJ, Bhatia V, Gerstner A, deFord J, Papaconstantinou J (2004) Gene expression analysis in mitochondria from chagasic mice: Alterations in specific metabolic pathways. Biochemical J 381 : 743–752. 15101819

61. Wen J-J, Gupta S, Guan Z, Dhiman M, Condon D, et al. (2010) Phenyl-alpha-tert-butyl-nitrone and benzonidazole treatment controlled the mitochondrial oxidative stress and evolution of cardiomyopathy in chronic chagasic rats. J Am Coll Cardiol 55 : 2499–2508. doi: 10.1016/j.jacc.2010.02.030 20510218