Günümüzde Biyoteknolojik Bakteriyel Aşılar

Öz

Aşılama infeksiyon hastalıklardan korunmak için en önemli ve maliyeti düşük yöntemlerden biridir. İnaktif ve atenüe aşılar, ekonomik öneme sahip hayvancılık sektörüne özgü ve zoonotik infeksiyonlarla mücadelede etkin araçlardır. Ancak, moleküler biyoloji ve immunolojide gerçekleştirilen gelişmelere bağlı olarak daha etkin ve güvenilir aşıların geliştirilmesine yönelik önemli çalışmalar yapılmakta ve yeni teknolojilere dayalı ürünler ticari kullanıma sunulmaktadır. Bu çerçevede, son yıllarda geliştirilen biyoteknolojik aşılar; natif ve rekombinant protein subunit, DNA ve vektör aşılardır. Subunit aşıların koruyucu immun yanıtı etkin uyarabilmesi için diğer inaktif aşılarda olduğu gibi uygun adjuvantlara ihtiyaç duyulmakta ve birden fazla immunojenden oluşan çok komponentli aşıların kullanımı önerilmektedir. DNA aşıları daha güçlü hücresel immun yanıt oluşturmakta ve genel olarak adjuvant ilavesi olmaksızın kullanılabilmektedir. Rekombinant subunit, DNA ve vektör aşıları etkindir ve daha az yan etkilidir, ayrıca marker olarak kullanım potansiyeline sahiptir. Marker aşıların en önemli yararları kontrol-eradikasyon programlarında aşılı ve infekte hayvanların ayrımını sağlayabilmeleridir. Özellikle, endemik seyreden infeksiyonlarla mücadelede yeni teknolojilere dayalı koruyucu antijenler ve aşılar ile adjuvantlar günümüz ve gelecek on yılın en önemli bilimsel, teknolojik ve ekonomik faaliyet alanlarından birini oluşturmaktadır. Bu çerçevede, yeni teknolojilere dayalı etkin, güvenilir, kolay uygulanabilir ve düşük maliyetli aşı geliştirme ve üretim çalışmaları veteriner hekimlik ve halk sağlığı açısından büyük öneme sahiptir.

Anahtar Kelimeler

• Bakteriyel aşılar, DNA aşı, marker aşı, subunit aşı, vektör aşı

Kaynakça

1. Al-Mariri A., Tibor A., Mertens P., Bolle XD., Michel P., Godefroid J., Walravens K., Letesson JJ., 2001. Protection of BALB/c Mice against Brucella abortus 544 Challenge by Vaccination with Bacterioferritin or P39 Recombinant Proteins with CpG Oligodeoxynucleotides as Adjuvant. Infect. Immun., 69, 4816-4822.
2. Anonim. 2009. OIE, Manual of Diagnostic Tests and Vaccines http://www.oie.int/Eng/normes/mmanual/A_i ndex.htm *Erişim tarihi: 02.06.2010+. Animals.
3. Barnet PV., Pullen L., Williams L., Doel T., 1996. International bank for foot-and-mouth disease vaccine: assessment of Montanide ISA 25 and ISA 206, two commercially available oil adjuvants. Vaccine, 14, 1187–1196.
4. Bae KD., Choi JY., Jang YS., Ahn SJ., Hur BK., 2009. Innovative vaccine production technologies: The evolution and value of vaccine production technologies. Arch. Pharm. Res. 32, 465-480.
5. Capozzo AVE., Cuberos L., Levine MM., Pasetti MF., 2004. Mucosally Delivered Salmonella Live Vector Vaccines Elicit Potent Immune Responses against a Foreign Antigen in Neonatal Mice Born to Naive and Immune Mothers. Infect. Immun., 72, 4637–4646.
6. Carey AJ., Timms P., Rawlinson G., Brumm J., Nilsson K., Harris JM., Beagley KW., 2010. A multi-subunit Chlamydial vaccine induces antibody and cell-mediated immunity in immunized Koalas (Phascolarctos cinereus): Comparison of three different adjuvants. Am. J. Reprod. Immunol., 63, 161-172.
7. Cassataro J., Velikovsky CA., Barrera S., Estein SM., 2005. A DNA vaccine coding for the Brucella outer protection against B. melitensis and B. ovis infection by eliciting a specific cytotoxic response. Infect. Immun. 73, 6537-6546.
8. Chen AY., Fry SR., Forbes-Faulkner J., Daggard G., Mukkur TK., 2006. Evaluation of the immunogenicity of the P97R1 adhesin of Mycoplasma hyopneumoniae as a mucosal vaccine in mice. J. Med. Microbiol., 55, 923– 929.

9. Cloeckaert A., Jacques I., Grilló MJ., Mar´ın CM., Grayon M., Blasco JM., Verger JM., 2004. Development and evaluation as vaccines in mice of Brucella melitensis Rev.1 single and double deletion mutants of the bp26 and omp31 genes coding for antigens of diagnostic significance in ovine brucellosis. Vaccine, 22, 2827-2835.
10. Dhama K., Mahendran M., Gupta PK., Rai A., 2008. DNA vaccines and their applications in veterinary practice: current perspectives Vet. Res. Commun., 32, 341–356.
11. Dunham SP., 2002. The application of nucleic acid in veterinary medicine. Res.Vet. Sci., 73, 9-16.
12. Eldridge JH., Staas JK., Meulbroek JA., Tice TR., 1991. Gilley biocompatible microspheres staphylococcal enterotoxin B toxoid which enhances the level of toxin-neutralizing antibodies. Infect. Immun. 59, 2978–2986. and an adjuvant for
13. Fensterle J., Grode L., Hess J., Kaufmann SH., 1999. Effective DNA vaccination against listeriosis by prime/boost inoculation with the gene gun. J. Immunol. 163, 4510–4518.
14. Grode L., Kursar M., Fensterle J., Kaufmann SHE., Hess, J., 2002. Cell mediated immunity induced by recombinant Mycobacterium bovis Bacille Calmette-Guerin strains against an intracellular bacterial pathogen: importance of antigen secretion or membrane-targeted antigen display as lipoprotein for vaccine efficacy. J. Immunol., 168, 1869-1876.
15. Guris D., Strebel PM., Jafari H., Wharton M., Hadler SC., 1997. Pertussis vaccination: Use of acellular pertussis vaccines among infants and young children CDC, MMWR, 46, 1-25.
16. Gurunathan S., Wu CY., Freidag BL., Seder RA., 2000. DNA vaccines: a key for inducing long- term cellular immunity. Curr. Opin. Immunol., 12, 442–447.
17. Hahn UK., Aichler M., Boehm R., Beyer W., 2006. Comparison of the immunological memory after DNA vaccination and protein vaccination against anthrax in sheep. Vaccine, 24, 4595– 4597.
18. Henderson LM., 2005. Overview of marker vaccine and differential diagnostic test technology. Biologicals, 33, 203-209.
19. Jacques I., Verger JM., Laroucau K., Grayon M., Vizcaino N., Peix A., Cortade F., Carreras F., Guilloteau LA., 2007. Immunological response and protective efficacy against Brucella melitensis induced by bp26 and omp31 B. melitensis Rev.1 deletion mutants in sheep. Vaccine, 25,.794-805.
20. Koff RS., 2002. Immunogenicity of hepatitis B vaccines: implications of immune memory. Vaccine. 20: 3695-3701.
21. Kurar, E. and Splitter, G.A., 1997. Nucleic acid vaccination of Brucella abortus ribosomal L7/L12 gene elicits immune response. Vaccine, 15, 1851–1857.
22. Liljeqvist S, Stahl S., 1999. Production of subunit recombinant immunogens, live delivery systems and nucleic acid vaccines. J. Biotechnol., 73, 1–33.
23. Lindblad EB., 2004. Aluminium compounds for use in vaccines. Immunol. Cell. Biol., 82, 497-505.
24. Lucas AH. , Reason DC., 1999. Polysaccharide vaccines as probes of antibody repertoires in man. Immunol. Rev., 171: 89-104.
25. Meeusen ENT.,Walker J., Peters A., Pastoret PP., Jungersen G., 2007. Current status of veterinary vaccines. Clin. Microbiol. Rev., 20, 489-510.
26. Nayak AR., Tinge SA., Tart RC., McDaniel LS., Briles DE.,Curtiss R. III., 1998. A live Recombinant avirulent oral Salmonella vaccine expressing pneumococcal surface protein A induces protective responses against Streptococcus pneumoniae. Infect. Immun., 66, 3744-3751.
27. Nour El-Din AN., Shkreta L., Talbot BG., Diarra MS., Lacasse P., 2006. DNA immunization of dairy cows with the clumping factor A of Staphylococcus aureus. Vaccine, 24, 1997– 2006.
28. O’Hagan DT, MacKichan ML, Singh M., 2001. Recent developments in adjuvants for vaccines against infectious diseases Biomol. Engineer., 18, 69–85.
29. Oliveira SC., Splitter GA., 1996. Immunization of mice with recombinant L7/L12 ribosomal protein confers protection against Brucella abortus infection. Vaccine, 14, 959-962.
30. Onate AA., Cespedes S., Cabrera A., Rivers R., Gonzalez A., Munoz C., Folch H., Andrews E., 2003. A DNA vaccine encoding Cu,Zn Superoxide dismutase of Brucella abortus induces protective immunity in BALB/c mice. Infect. Immun. 71:4857-4861.
31. Özcengiz E., Kılınç K., Büyüktanır Ö., Günalp A. 2004. Rapid purification of pertussis toxin (PT) and filamentous hemagglutinin (FHA) by cation- exchange chromatography. Vaccine, 22, 1570- 1575.
32. Perrie Y., Mohammed AR., Kirby DJ., McNeil SE., Bramwell VW., 2008. Vaccine adjuvant systems: Enhancing the efficacy of sub-unit protein antigens Int. J. Pharm., 364, 272–280.
33. Sangari FJ., Garcia-Lobo JM., Agüero J., 1994. The Brucella abortus vaccine strain B19 carries a deletion in the erythritol catabolic genes. FEMS. Microbiol. Lett. 121, 337-342.
34. Schurig GG., Sriranganathan N., Corbel MJ., 2002. Brucellosis vaccines: past, present and future. Vet. Microbiol. 90, 479–496.
35. Sechi LA., Mara L., Cappai P., Frothingam R., Ortu S., Leoni A., Ahmed N., Zanetti S., 2006. Immunization with DNA vaccines encoding different mycobacterial antigens elicits a Th1 type immune response in lambs and protects against Mycobacterium avium subspecies paratuberculosis infection. Vaccine, 24, 229– 235.
36. Shams H., 2005. Recent developments in veterinary vaccinology. Vet. J. 170, 289–299.
37. Singh M, O’Hagan DT., 2003. Recent advances in veterinary vaccine adjuvants. Int. J. Parasitol., 33, 469–478.
38. Strube W., Auer S., Block W., Heinen E., Kretzdorn D., Rodenbach C., Schmeer N., 1996. A gE deleted infectious bovine rhinotracheitis marker vaccine for use in improved bovine herpesvirus Microbiol., 53, 181-189. programs. Vet.
39. Sutter G., Moss B., 1992. Non-replicating vaccinia vector efficiently expresses recombinant genes. PNAS-USA 89, 10847-10851.
40. Tollis M., 2006. Standardization or tailorization of veterinary vaccines: a conscious endeavour against infectious disease of animals Ann. Ist. Super. Sanità, 42, 446-449.
41. Valenzuela P., Medina A., Rutter W.J., Ammerer G., Hall BD., 1982. Synthesis and assembly of hepatitis B virus surface antigen particles in yeast. Nature 298, 347-350.
42. Vanniasinkam, T., Barton, M.D. and Heuzenroeder, M.W., 2005. Immune response to vaccines based upon the VapA protein of the horse pathogen, Rhodococcus equi, in a murine model. International Journal of Medical Microbiology, 294, 437–445
43. Yang X., Hudson M., Walters N., Bargatze RF., Pascual DW., 2005. Selection of protective epitopes for Brucella melitensis by DNA vaccination. Infect Immun., 73, 7297-7303.
44. Yang X., Walters N., Robison A., Trunkle T., Pascual DW., recombinant Brucella melitensis bp26 and trigger factor with cholera toxin reduces B. melitensis colonization. Vaccine, 25, 2261- 2268. immunization with
45. Yu DH., Hu XD., Cai H., 2007. A combined DNA vaccine encoding BCSP31, SOD, and L7/L12 confers high protection against Brucella abortus 2308 by inducing specific CTL responses. DNA Cell Biol. 26, 435-43.