Email this article A COMPARATIVE CHARACTERISTIC OF ANTIGENIC PROPERTIES OF RECOMBINANT AND NATIVE HBS-ANTIGENS WITH G145R MUTATION AND EVALUATION OF THEIR IMMUNOGENICITY
- Authors: Konopleva M.V.1, Borisova V.N.2, Sokolova M.V.1, Feldsherova A.A.1, Krymskij M.A.2, Semenenko T.A.1, Suslov A.P.1
-
Affiliations:
- Federal Research Center of Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya
- ZAO NPK Combiotech
- Issue: Vol 62, No 4 (2017)
- Pages: 179-186
- Section: ORIGINAL RESEARCH
- Submitted: 20.01.2020
- Published: 20.08.2017
- URL: https://virusjour.crie.ru/jour/article/view/164
- DOI: https://doi.org/10.18821/0507-4088-2017-62-4-179-186
- ID: 164
Cite item
Full Text
Abstract
Background: One of the important reasons for spreading of hepatitis B virus (HBV) under conditions of vaccine pressure is emergence of escape mutations. Prevalent G145R mutation in S-gene leads to the most expressed changes of serological properties of HBV. Consequently, HBsAg is modified so thoroughly that it cannot be recognized by the majority of anti-HBs. Mutant G145R also differs from a wild type HBsAg by its immunogenic properties. At present, the relevance of enhancement of hepatitis B vaccine in view of mutant virus variants has been recognized. Objectives: a comparative study of antigenic and immunogenic properties of native and recombinant G145R mutants and an estimation of possibility for developing antigenic component of hepatitis B vaccine with G145R mutation in HBsAg. Methods: antigenic properties of recombinant HBsAg with G145R mutation were compared with each other and with native mutants by serological fingerprinting method. Then, BALB/c mice and sheep were immunized with selected recombinant antigen under different protocols. Titers of antibodies specific to wild type or mutant G145R type of HBsAg in sera of immunized animals were measured. Results: it was found that not all the recombinant HBsAg variants with G145R substitution have the same antigenic properties as native HBsAg with similar mutation. Recombinant HBsAg selected according to the principle of antigenic similarity possesses immunogenicity in mice and sheep causing the production of antibodies reacting with native wild and mutant type HBsAg. It was shown that mutant antigen is less immunogenic, requires larger doses and more time for the development of immune response; however, it is capable of causing an antibody level comparable with wild type antigen. Conclusion: preliminary selection of recombinant HBsAg containing G145R mutation with antigenic and immunogenic properties similar to the native analogue creates the basis for development of a specific component of hepatitis B vaccine with escape mutation G145R in HBsAg.
Keywords
About the authors
M. V. Konopleva
Federal Research Center of Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya
Author for correspondence.
Email: maria-konopleva@rambler.ru
Россия
V. N. Borisova
ZAO NPK Combiotech
Email: noemail@neicon.ru
Россия
M. V. Sokolova
Federal Research Center of Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya
Email: noemail@neicon.ru
Россия
A. A. Feldsherova
Federal Research Center of Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya
Email: noemail@neicon.ru
Россия
M. A. Krymskij
ZAO NPK Combiotech
Email: noemail@neicon.ru
Россия
T. A. Semenenko
Federal Research Center of Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya
Email: noemail@neicon.ru
Россия
A. P. Suslov
Federal Research Center of Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya
Email: noemail@neicon.ru
Россия
References
- Blum H.E. Hepatocellular carcinoma: therapy and prevention. World J. Gastroenterol. 2005; 11(47): 7391-400.
- Weber B. Genetic variability of the S gene of hepatitis B virus: clinical and diagnostic impact. J. Clin. Virol. 2005; 32: 102-12.
- Ben-Porath E., Wands J.R., Marciniak R.A., Wong M.A., Hornstein L., Ryder R., et al. Structural analysis of hepatitis B surface antigen by monoclonal antibodies. J. Clin. Invest. 1985; 76(4): 1338-47.
- Roohi A., Khoshnoodi J., Zarnani A.H., Shokri F. Epitope mapping of recombinant hepatitis B surface antigen by murine monoclonal antibodies. Hybridoma (Larchmt). 2005; 24(2): 71-7.
- Waters J.A., Kennedy M., Voet P., Hauser P., Petre J., Carman W., et al. Loss of the Common “A” Determinant of Hepatitis B Surface Antigen by a Vaccine-induced Escape Mutant. J. Clin. Invest. 1992; 90: 2543-7.
- Zheng X., Weinbergerc K.M., Gehrked R., Isogawaa M., Hilkene G., Kempera T., et al. Mutant hepatitis B virus surface antigens (HBsAg) are immunogenic but may have a changed specificity. Virology. 2004; 329: 454-64.
- Ogata N., Zanetti A.R., Yu M., Miller R.H., Purcell R.H. Infectivity and Pathogenicity in Chimpanzees of a Surface Gene Mutant of Hepatitis B Virus that Emerged in a Vaccinated Infant. J. Infect. Dis. 1997; 175(3): 511-23.
- Carman W.F., Zanetti A.R., Karayiannis P., Waters J., Manzillo G., Tanzi E., et al. Vaccine-induced escape mutant of hepatitis B virus. Lancet. 1990; 336: 325-9.
- Баженов А.И., Эльгорт Д.А., Фельдшерова А.А., Будницкая П.З., Никитина Г.И., Хац Ю.С. и др. Выявление антител к мутантным формам HBsAg у лиц иммунизированных против гепатита В вакцинами разных субтипов. Эпидемиология и Вакцинопрофилактика. 2011; (5): 49-53.
- Баженов А.И., Эльгорт Д.А., Фельдшерова А.А., Будницкая П.З., Никитина Н.И., Хац Ю.С. и др. Сравнительная оценка активности анти-HBs, индуцированных естественным путём или вакцинацией, в отношении различных вариантов HBsAg. Эпидемиология и Вакцинопрофилактика. 2012; (2): 76-81.
- Zuckerman A.J., Zuckerman J.N. Molecular epidemiology of hepatitis B virus mutant. J. Med. Virol. 1999; 58: 193-5.
- Kniskern P.J. HBsAg escape mutant vaccine. Patent EP № 0 511 855 A1; 1992.
- Kniskern P.J. A multivalent hepatitis B virus vaccine. Patent EP № 0 533 263 A2; 1992.
- Thomas H.C., Carman W.F. Hepatitis B vaccine. Patent US 5.639.637; 1997.
- Крымский М.А., Борисов И.А., Яковлев М.С., Агафонов М.О., Тер-Аванесян М.Д., Суслов А.П. и др. Рекомбинантный штамм дрожжей Hansenula polymorpha - продуцент мутантного поверхностного антигена вируса гепатита В (варианты). Патент РФ № 2586513 C1; 2016.
- Баженов А.И., Коноплева М.В., Эльгорт Д.А., Фельдшерова А.А., Хац Ю.С., Годков М.А. и др. Алгоритм серологического поиска и оценка распространенности серологически значимых HBsAg-мутаций у хронических носителей вируса гепатита В. Журнал микробиологии, эпидемиологии и иммунобиологии. 2007; (6): 30-7.
- Tijssen P., Kurstak E. Highly efficient and simple methods for the preparation of peroxidase and active peroxidase-antibody conjugates enzyme immunoassays. Anal. Biochem. 1984; 136(2): 451-7
- Крымский М.А., Борисов И.А., Яковлев М.С., Мельников В.А., Суслов А.П., Семененко Т.А. и др. Способ оценки уровня антител, специфичных к различным вариантам HBsAg вируса гепатита В. Патент РФ № 2616236C1; 2017
- Bellecave P., Gouttenoire J., Gajer M., Brass V., Koutsoudakis G., Blum H.E., et al. Hepatitis B and C virus coinfection: a novel model system reveals the absence of direct viral interference. Hepatology. 2009; 50(1): 46-55
Supplementary files
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).