Muhammed Ahmed SELÇUK, Figen ÇELİK, Sami ŞİMŞEK

Parazitoloji’de DNA Aşı Çalışmaları

Paraziter hastalıklar, dünya çapında insan ve hayvan sağlığında çok önemli bir yer işgal etmektedir. Paraziter enfeksiyonların kontrolü ve önlenmesinde parazit yükünün azaltılması çok önemli bir hedeftir ancak tek başına uygulanamaz. Bu nedenle, sadece parazit yükünü değil aynı zamanda parazit bulaşma riskini de azaltmak için çevresel ve ekolojik değişikliklerin uygulanması gerekmektedir. Aşılar en etkili, güvenilir ve sürdürülebilir yöntemlerdir ve bu açıdan paraziter hastalıkları kontrol etmek için alternatif çözümler olarak da düşünülmektedir. Bu amaçla farmakolojik ilaçlar ve pestisitlerin kullanımına olan bağımlılığı da azaltmada faydalıdırlar. DNA aşılaması, immünolojik bir yanıt üretmek için genetik olarak tasarlanmış olan DNA'yı kullanan yeni bir teknolojik metoddur. Bu amaca ulaşmak için önemli bir strateji, üzerlerinde kodlanmış antijenlere sahip DNA plazmidlerini kullanmaktır. Bu antijen kodlayan DNA plazmidi, parazitlere, bakterilere ve hastalık üreten virüslere karşı humoral ve hücresel bağışıklık tepkisini indükleyebilir niteliktedir. DNA aşıları, günümüzde gelişmekte olan bir subunit aşı türüdür. Bu derlemede, DNA aşılarının üretim ve etki mekanizmaları hakkında detaylı bilgiler verilmiş, paraziter hastalıklara karşı yapılan DNA aşı çalışmaları hakkında bilgiler sunulmuştur.

DNA Vaccine Studies in Parasitology

Parasitic diseases occupy a very important place in human and animal health worldwide. Reducing the parasite load is a very important goal in the control and prevention of parasitic infections, but it cannot be applied alone. Therefore, environmental and ecological changes need to be implemented to reduce not only the parasite load but also the risk of parasite transmission. Vaccines are the most effective, safe and sustainable methods, and in this regard, they are also considered as alternative solutions to control parasitic diseases and are useful in reducing dependence on pharmacological drugs and the use of pesticides. DNA vaccination is a new technological method that uses genetically engineered DNA to generate an immunological response. An important strategy to achieve this goal is to use DNA plasmids with encoded antigens on them. This antigen-encoding DNA plasmid is capable of inducing the humoral and cellular immune response against parasites, bacteria and disease-producing viruses. DNA vaccines are a type of subunit vaccine currently in development. In this review, detailed information about the production and mechanism of action of DNA vaccines is given, and information about DNA vaccine studies against parasitic diseases is presented.

PDF

___

1. Battegay M, Mössner J, Parasitic diseases. Der Internist 2006; 47: 785-785.
2. Edwards G, Krishna S. Pharmacokinetic and pharmacodynamic issues in the treatment of parasitic infections. Eur J Clin Microbiol Infect Dis 2004; 23: 233- 42.
3. Behr C, da Silva LHP, Vaccination against protozoa. In: Mehlhorn H. (Editor). Encyclopedia of Parasitology. Berlin, Heidelberg: Springer, 2016.
4. Sharman PA, Smith NC, Wallach MG, Katrib M. Chasing the golden egg: Vaccination against poultry coccidiosis. Parasite Immunol 2010; 32: 590-8.
5. Ramaswamy K, Role of parasite vaccines in sustained animal health and production. J Vet Parasitol 2015; 29: 73-83.
6. Hobernik D, Bros M. DNA vaccines how far from clinical use? Int J Mol Sci 2018; 19: 3605.
7. Kutzler MA, Weiner DB. DNA vaccines: Ready for prime time? Nat Rev Genet 2008; 9: 776-788.
8. Li S, MacLaughlin FC, Fewell JG, et al. Muscle-specific enhancement of gene expression by incorporation of SV40 enhancer in the expression plasmid. Gene Ther 2001; 8: 494-497.
9. Shedlock DJ, Weiner DB. DNA vaccination: Antigen presentation and the induction of immunity. J Leukoc Biol 2000; 68: 793-806.
10. Williams JA, Carnes AE, Hodgson CP. Plasmid DNA vaccine vector design: Impact on efficacy, safety and upstream production. Biotechnol Adv 2009; 27: 353-370.
11. Capone S, Zampaglione I, Vitelli A, et al. Modulation of the immune response induced by gene electrotransfer of a hepatitis C virus DNA vaccine in nonhuman primates. J Immunol 2006; 177: 7462-7471.
12. Smooker PM, Steeper KR, Drew DR, Strugnell RA, Spithill TW. Humoral responses in mice following vaccination with DNA encoding glutathione S‐transferase of Fasciola hepatica: effects of mode of vaccination and the cellular compartment of antigen expression. Parasite Immunol 1999; 21: 357-364.
13. Kofta W, Mieszczanek J, Płucienniczak G, Wędrychowicz H. Successful DNA immunisation of rats against fasciolosis. Vaccine 2000; 18: 2985-2990.
14. Smooker PM, Kennedy NJ, Steeper KR, Christopoulos H, Spithill TW. Fasciola: Kinetics and quality of humoral responses to fatty acid binding protein and cathepsin l following delivery as DNA vaccines in mice. Exp Parasitol 2001; 97: 154-160.
15. Wedrychowicz H, Szymanski P, Panasiuk LJ, Bienkowska-Szewczyk K. Humoral immune response of rats vaccinated with cDNA or protein form of glutathioneS-transferase of Fasciola hepatica to infection with metacercariae of the fluke. Helminthologia 2002; 39: 127- 33.
16. Wedrychowicz H, Lamparska M, Kesik M, et al. The immune response of rats to vaccination with the cDNA or protein forms of the cysteine proteinase of Fasciola hepatica. Vet Immunol Immunopathol 2003; 94: 83-93.
17. Espino AM, Osuna A, Gil R, Hillyer GV. Fasciola hepatica: Humoral and cytokine responses to a member of the saposin-like protein family following delivery as a DNA vaccine in mice. Exp Parasitol 2005; 110: 374-383.
18. Espino AM, Morales A, Delgado B, et al. Partial immunity to Fasciola hepatica in mice after vaccination with FhSAP2 delivered as recombinant protein or DNA construct. Ethn Dis 2010; 20: S1.
19. Jayaraj R, Piedrafita D, Spithill T, Smooker P. Evaluation of the immune responses induced by four targeted DNA vaccines encoding the juvenile liver fluke antigen, cathepsin B in a mouse model. Gen Vac Ther 2012; 10: 1-9.
20. Medlock JM, Hansford KM, Bormane A, et al. Driving forces for changes in geographical distribution of Ixodes ricinus ticks in Europe. Parasite Vector 2013; 6:1-1.
21. Zhang Y, Taylor MG, Johansen MV, Bickle QD. Vaccination of mice with a cocktail DNA vaccine induces a Th1-type immune response and partial protection against Schistosoma japonicum infection. Vaccine 2001; 20: 724-730.
22. Lei N, Liu FC, Ren CP, Shen JJ, Liu M. An Efficient Schistosoma japonicum bivalent membrane protein antigen DNA vaccine against schistosomiasis in mice. Med Sci Monit: Int Med J Exp Clin Res 2019; 25: 9319.
23. Frantz FG, Ito T, Cavassani KA, et al. Therapeutic DNA vaccine reduces schistosoma mansoni–induced tissue damage through cytokine balance and decreased migration of myofibroblasts. Am J Pathol 2011; 179: 223- 229.
24. Chlichlia K, Bahgat M, Ruppel A, Schirrmacher V. DNA vaccination with asparaginyl endopeptidase (Sm32) from the parasite Schistosoma mansoni: Anti-fecundity effect induced in mice. Vaccine 2001; 20: 439-447.
25. Lightowlers MW, Rolfe R, Gauci CG. Taenia saginata: Vaccination against cysticercosis in cattle with recombinant oncosphere antigens. Exp Parasitol 1996; 84: 330-338.
26. Guo YJ, Sun SH, Zhang Y, et al. Protection of pigs against Taenia solium cysticercosis using recombinant antigen or in combination with DNA vaccine. Vaccine 2004; 22: 3841-3847.
27. Drew DR, Lightowlers MW, Strugnell RA. A comparison of DNA vaccines expressing the 45W, 18k and 16k hostprotective antigens of Taenia ovis in mice and sheep. Vet Immunol Immunopathol 2000; 76: 171-181.
28. Azizi H, Kazemi B, Bandehpour M, et al. Modulation of the immune response to DNA Vaccine encoding gene of 8-kda subunit of Echinococcus granulosus antigen B using murine interleukin-12 plasmid in BALB/c mice. Iranian J Parasitol 2016; 11: 480.
29. Han K, Xu L, Yan R, Song X, Li X. Vaccination of goats with glyceraldehyde-3-phosphate dehydrogenase DNA vaccine induced partial protection against Haemonchus contortus. Vet Immunol Immunopathol 2012; 149: 177- 185.
30. Wiśniewski M, Jaros S, Bąska P, Cappello M, Wędrychowicz H. Ancylostoma ceylanicum metalloprotease 6 DNA vaccination induces partial protection against hookworm challenge infection. Acta Parasitol 2013; 58: 376-383.
31. Kerepesi LA, Keiser PB, Nolan TJ, et al. DNA immunization with Na+-K+ ATPase (Sseat-6) induces protective immunity to larval Strongyloides stercoralis in mice. Infect Immun 2005; 73: 2298-2305.
32. Chen N, Yuan ZG, Xu MJ, et al. Ascaris suum enolase is a potential vaccine candidate against ascariasis. Vaccine 2012; 30: 3478-3482.
33. Malheiro A, Aníbal FF, Martins-Filho OA, et al. pcDNA-IL12 vaccination blocks eosinophilic inflammation but not airway hyperresponsiveness following murine Toxocara canis infection. Vaccine 2008; 26: 305-315.
34. Li BW, Rush A, Zhang SR, Curtis KC, Weil GJ. Antibody responses to Brugia malayi antigens induced by DNA vaccination. Filaria Journal 2004; 3: 1-8.
35. Steisslinger V, Korten S, Brattig NW, Erttmann KD. DNA vaccine encoding the moonlighting protein Onchocerca volvulus glyceraldehyde-3-phosphate dehydrogenase (Ov-GAPDH) leads to partial protection in a mouse model of human filariasis. Vaccine 2015; 33: 5861-5867.
36. Yang Y, Zhang Z, Yang J, et al. Oral vaccination with Ts87 DNA vaccine delivered by attenuated Salmonella typhimurium elicits a protective immune response against Trichinella spiralis larval challenge. Vaccine 2010; 28: 2735-2742.
37. Kurup SP, Tewari AK. Induction of protective immune response in mice by a DNA vaccine encoding Trypanosoma evansi beta tubulin gene. Vet Parasitol 2012; 187: 9-16.
38. Limon-Flores AY, Cervera-Cetina R, Tzec-Arjona JL, et al. 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 2010; 28: 7414-7419.
39. Silva MS, Prazeres DM, Lança A, Atouguia J, Monteiro GA. Trans-sialidase from Trypanosoma brucei as a potential target for DNA vaccine development against African trypanosomiasis. Parasitol Res 2009; 105: 1223- 1229.
40. Ahmed SB, Bahloul C, Robbana C, Askri S, Dellagi K. A comparative evaluation of different DNA vaccine candidates against experimental murine leishmaniasis due to L. major. Vaccine 2004; 22: 1631-1639.
41. Aguilar-Be I, da Silva Zardo R, Paraguai de Souza E, et al. Cross-protective efficacy of a prophylactic Leishmania donovani DNA vaccine against visceral and cutaneous murine leishmaniasis. Infect Immun 2005; 73: 812-9.
42. Oliveira-da-Silva JA, Lage DP, Ramos FF, et al. Leishmania infantum pyridoxal kinase evaluated in a recombinant protein and DNA vaccine to protects against visceral leishmaniasis. Mol Immunol 2020; 124: 161-171.
43. Abdul-Wahid A, Faubert G. Mucosal delivery of a transmission-blocking DNA vaccine encoding Giardia lamblia CWP2 by Salmonella typhimurium bactofection vehicle. Vaccine 2007; 25: 8372-8383.
44. Yu Q, Li J, Zhang X, et al. Induction of immune responses in mice by a DNA vaccine encoding Cryptosporidium parvum Cp12 and Cp21 and its effect against homologous oocyst challenge. Vet Parasitol 2010; 172: 1- 7.
45. Song X, Ren Z, Yan R, Xu L, Li X. Induction of protective immunity against Eimeria tenella, Eimeria necatrix, Eimeria maxima and Eimeria acervulina infections using multivalent epitope DNA vaccines. Vaccine 2015; 33: 2764-2770.
46. Scorza T, D'souza S, Laloup M, et al. A GRA1 DNA vaccine primes cytolytic CD8+ T cells to control acute Toxoplasma gondii infection. Infect Immun 2003; 71: 309- 316.
47. Liu S, Shi L, Cheng YB, et al. Evaluation of protective effect of multi-epitope DNA vaccine encoding six antigen segments of Toxoplasma gondii in mice. Parasitol Res 2009; 105: 267-274.
48. Cesbron-Delauw MF. Dense-granule organelles of Toxoplasma gondii: Their role in the host-parasite relationship. Parasitol Today 1994; 10: 293-296.
49. Ismael AB, Hedhli D, Cérède O, et al. Further analysis of protection induced by the MIC3 DNA vaccine against T. gondii: CD4 and CD8 T cells are the major effectors of the MIC3 DNA vaccine-induced protection, both Lectin-like and EGF-like domains of MIC3 conferred protection. Vaccine 2009; 27: 2959-2966.
50. Cong H, Gu QM, Yin HE, et al. Multi-epitope DNA vaccine linked to the A2/B subunit of cholera toxin protect mice against Toxoplasma gondii. Vaccine 2008; 26: 3913- 3921.
51. Dautu G, Munyaka B, Carmen G, et al. Toxoplasma gondii: DNA vaccination with genes encoding antigens MIC2, M2AP, AMA1 and BAG1 and evaluation of their immunogenic potential. Exp Parasitol 2007; 116: 273- 282.
52. Mohamed RM, Aosai F, Chen M, et al. Induction of protective immunity by DNA vaccination with Toxoplasma gondii HSP70, HSP30 and SAG1 genes. Vaccine 2003; 21: 2852-2861.
53. Yu G, Liang W, Yang Q, et al. Immune protective evaluation elicited by DNA vaccination with Neospora caninum dense granules proteins in mice. Front Vet Sci 2021; 8: 42.
54. McConkey SJ, Reece WH, Moorthy VS, et al. Enhanced T-cell immunogenicity of plasmid DNA vaccines boosted by recombinant modified vaccinia virus Ankara in humans. Nat Med 2003; 9: 729-735.
55. Bojang KA, Milligan PJ, Pinder M, et al. Efficacy of RTS, S/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: A randomised trial. The Lancet 2001; 358: 1927-1934.
56. Stoute JA, Kester KE, Krzych U, et al. Long-term efficacy and immune responses following immunization with the RTS, S malaria vaccine. J Infect Dis 1998; 178: 1139- 1144.
57. Ballou WR. The development of the RTS, S malaria vaccine candidate: challenges and lessons. Parasit Immunol 2009; 31: 492-500.
58. Carroll JE. Babesia microti Recombinant DNA Vaccine as a Model for Babesia bovis Prevention (PhD dissertation, Texas A & M University), 2011.
59. Crosby FL, Lundgren AM, Hoffman C, Pascual DW, Barbet AF. VirB10 vaccination for protection against Anaplasma phagocytophilum. BMC Microbiol 2018; 18: 1- 2.
60. Klouwens MJ, Trentelman JJ, Wagemakers A, et al. Ticktattoo: DNA vaccination against B. burgdorferi or Ixodes scapularis tick proteins. Front Immunol 2021; 12.
61. Zhang TT, Zhang JC, Cui XJ, et al. Evaluation of immune protection induced by DNA vaccines from Haemaphysalis longicornis paramyosin in rabbits. Parasit Vectors 2017; 10: 1-6.
62. Giese S, Giese M. Oral Vaccination of Honeybees Against Varroa destructor. Mol Vaccines. Springer 2013; 269-278.
63. Gu X, Xie Y, Wang S, Peng X, Lai S, Yang G. Immune response induced by candidate Sarcoptes scabiei var. cuniculi DNA vaccine encoding paramyosin in mice. Exp Appl Acar 2014; 63: 401-412.
64. Bai HY, Liu CX, Huhe B, Wang WL. Construction of Hypoderma lineatum Hypodermin C gene eukaryotic expression plasmid and ımmune tests in mice. Progress Vet Med 2012: 08.