Antibody response to Hepatitis B surface antigen displayed on filamentous phage

Year 2017, Volume: 5 Issue: 2, 124 - 134, 25.12.2017

Aynur Başalp , İbrahim Hatipoğlu Bertan Koray Balcıoğlu İbrahim Söğüt , Aylin Özdemir Bahadir , Kamil Serkan Uzyol Hülya Sivas , Berrin Erdağ

https://doi.org/10.24998/maeusabed.322704

Abstract

Phages are highly
immunogenic molecules capable of inducing both humoral and cellular immune
response and have been used as potential vaccine delivery vehicles. In this
study, the full-length Hepatitis B surface antigen (HBsAg) was expressed as HBsAg-pIII
fusion protein on M13 phage and the efficiacy of recombinant phage was studied
in BALB/cJ mice. It was shown that, immunization of mice with the highest dose
of recombinant phage (10¹²) generated an increased antibody response
compared to wild type phage immunization. After having a promising result in
BALB/cJ mice, recombinant phage was tested in Hepatitis B virus (HBV)
transgenic mice and hybrid mice (C57BL/6JXBALB/c) and
its effect was also compared with the well known adjuvants such as alum and
mineral oil adjuvants. Our results have shown that immunization of BALB/cJ
mice, HBV transgenic mice and hybrid mice with recombinant phage elicited an antigen-specific
antibody response. The results also indicated that very strong adjuvants/carriers
should be used to induce immune response in HBV carriers.

Keywords

Adjuvant, Antibody response, Hepatitis B Virus, Phage display

Filamentöz faj üzerinde eksperese edilen Hepatit B yüzey antijenine karşı antikor yanıtı

Abstract

Fajlar organizmada
humoral ve hücresel  immün yanıtı
uyandırabilen yüksek immünojenik özelliğe sahip moleküllerdir ve potansiyel aşı
taşıyıcısı olarak kullanılmaktadırlar. Bu çalışmada Hepatit B yüzey antijeni (HBsAg)
tam molekül olarak M13 faj yüzeyinde füzyon protein olarak ekprese edilmiş ve
rekombinant fajın antijenik etkisi BALB/cJ farelerinde incelenmiştir. Farelerin
yüksek dozda (10¹²)  rekombinant faj ile immünize edilmesinin normal
faja kıyasla daha yüksek antikor yanıtına neden olduğu gösterilmiştir. BALB/cJ
farelerinde elde edilen olumlu yanıt sonrası rekombinant fajın etkinliği
Hepatit B  virüsü (HBV) transgenik farelerde
ve hibrid farelerde (C57BL/6JXBALB/c) incelenmiş ve ayrıca etkisi alüminyum
adjuvantı ve mineral yağ adjuvantı gibi yaygın kullanımı olan adjuvantlarla
karşılaştırılmıştır. Çalışmanın sonuçları BALB/cJ farelerin, HBV transgenik farelerin
ve hibrid farelerin rekombinant faj ile immünizasyonunun antijene özgü antikor
yanıtı oluşturduğunu göstermiştir.  Sonuçlar ayrıca HBV taşıyıcılarında immün
yanıt oluşturmak için güçlü adjuvantların kullanılması gerektiğini de işaret
etmektedir. 

Keywords

Adjuvant, Antikor yanıtı, Hepatit B virüsü, Faj gösterim

References

• Referans1. Ambrosch F, Wiedermann G, Kundi M et al. 2000. A hepatitis B vaccine formulated with a novel adjuvant system. Vaccine 18: 2095-2101
• Referans2. Bagis H, Arat S, Odaman HM et al. 2006.Stable Transmission and Expression of the Hepatitis B Virus Total Genome in Hybrid Transgenic Mice Until F10 Generation. J Exp Zool 305a: 420-427
• Referans3. Bahadir AO, Balcioglu BK, Uzyol KS et al. 2011. Phage displayed HBV core antigen with immunogenic activity. Appl Biochem Biotech 165:1437-1447
• Referans4. Bakhshinejad B, Sadeghizadeh M. 2014. Bacteriophages and their applications in the diagnosis and treatment of hepatitis B virus infection. World J Gastroenterol. 20(33): 11671-11683
• Referans5. Bantvala J, Van Damme P, Oehen S. 2001. Lifelong protection against hepatitis B: the role of vaccine immunogenicity in immune memory. Vaccine 19: 877- 885
• Referans6. Bastien N, Trudel M, Simard C. 1997. Protective Immune responses induced by the immunization of mice with a recombinant bacteriophage displaying an epitope of the Human Respiratory Syncytial Virus. Virology 234: 118-122
• Referans7. Bertoletti A, Gehring AJ. 2006. The immune response during hepatitis B virus infection. J Gen Virol 87: 1439-1449
• Referans8. Coffman RL, Sher A, Seder RA. 2010. Vaccine adjuvants: Putting innate immunity to work. Immunity 33: 492-503
• Referans9. Cooper PD, Turner R, McGovern J. 1991.Algammulin (gamma inulin/alum hybrid adjuvants) has a greater adjuvanticity than alum for hepatitis B surface antigens in mice. Immunol Lett 27: 131-134
• Referans10. Flach TL, Gilbert N, Hari A et al. 2011. Alum interaction with dendritic cell membrane lipids is essential for its adjuvanticity. Nat Med 17: 479-49
• Referans11. Gao J, Wang Y, Liu Z et al. 2010. Phage display and its application in vaccine design. Ann Microbiol 60: 13-19
• Referans12. Gregorio E, Tritto E, Rappuoli R. 2008. Alum adjuvanticity: unrevealing a century old mistery. Eur J Immunol 38: 2068-2071
• Referans13. Hong Y, Peng Y, Michael M et al. 2011. Lentivector expressing HBsAg and immunoglobulin Fc fusion antigen induces potent immune responses and results in seroconversion in HBsAg transgenic mice. Vaccine 29: 3909-3916
• Referans14. Kok WL, Yusoff K, Nathan S et al. 2002.Cloning, expression and display of the preS domain of hepatitis B virus on filamanetous bacteriophage M13. J Biochem Mol Biol Biophys 6: 55-58
• Referans15. Lambrecht BN, Kool M, Willart MAM et al. 2009. Mechanism of action of clinically approved adjuvants. Curr Opin Immunol 21: 23-29
• Referans16. Lindblad EB. 2004. Aluminum adjuvants in retrospect and prospect. Vaccine 22: 3658-3668
• Referans17. Marrack P, McKee AS, Munks MW. 2009.Towards an understanding of the adjuvant action of aluminum. Nat Rev Immunol 9: 287-293
• Referans18. Mastelic B, Garçon N, Guidice GD et al. 2013. Predictive markers of safety and immunogenicity of adjuvanted vaccines. Biologicals . 41: 458-468
• Referans19. Mc Cluskie MJ, Davis HL. 1998. CpG DNA is a potent enhancer of systemic and mucosal immune responses against hepatitis B surface antigen with intranasal administration to mice. Immunology 161: 4463-4466
• Referans20. Meola A, Delmastro P, Monaci P et al. 1995. Derivation of vaccines from mimotopes: Immunologic properties of human Hepatitis B Virus surface antigen mimotopes displayed on filamentous phage. J Immunol 154: 3162-3172
• Referans21. Minenkova OO, Ilyichev AA, Kishchenko GP et al. 1993.Design of specific immunogens using filamentous phage as the carrier. Gene 128: 85-88
• Referans22. Molenaar TJM, Michon I, Haas SAM et al. 2002. Uptake and processing of modified bacteriophage M13 in mice: implications for phage display. Virology 293: 182-191
• Referans23. Nellore RV, Pande PG, Young D et al. 1992. Evaluation of biodgredable microspheres as vaccine adjuvant for hepatitis B surface antigen. J Parent Sci Techn 46: 176-180
• Referans24. Pichichero ME. 2008.Improving vaccine delivery using novel adjuvant systems. Hum Vaccines 44: 262-270
• Referans25. Sidhu SS. 2001. Engineering M13 for phage display. Biomol Eng 18: 57-63
• Referans26. Smith GP. 1985. Filamantous fusion phage: Novel expression vectors that display cloned antigens on the virion surface. Science 228: 1315-1317
• Referans27. Solomon B. 2007. Active immunization against alzheimer’s ß-amyloid peptide using phage display technology. Vaccine 25: 3053-3056
• Referans28. Tan GH, Yusoff K, Seow HF et al. 2005.Antigenicity and immunogenicity of the immunodominant region of Hepatitis B surface antigen displayed on bacteriophage T7. J Med Virol 77: 475-480
• Referans29. Tan WS, Ho KL. 2014. Phage display creates innovative applications to combat hepatitis B virüs. World J Gastroenterol. 20(33): 11650-11670
• Referans30. Traquina P, Morandi M, Contorni M et al. 1996.MF59 Adjuvant enhances the antibody response to recombinant hepatitis B surface antigen vaccine in primates. J Infect Dis 174: 1168-1175
• Referans31. Van Houten NE, Zwick MB, Menendez A et al. 2006. Filamentous phage as an immunogenic carrier to elicit focused antibody responses against a synthetic peptide. Vaccine 24: 4188-4200
• Referans32. Wan Y, Wu Y, Bian J et al. 2001.Induction of hepatitis B virus-specific cytotoxic T lymphocytes response in vivo by filamentous phage display vaccine. Vaccine 19: 2918-2923
• Referans33. Yang Q, Wang L, Lu D et al. 2005. Prophylactic vaccination with phage-displayed epitope of C. albicans elicits protective immune responses against systemic candidiasis in C57BL/6 mice. Vaccine 23: 4088-4096
• Referans34. Zanetti AR, Van Damme P, Shouval D. 2008.The global impact of vaccination against hepatitis B: A historical overview. Vaccine 26: 6266-6273