IMMUNOGENICITY OF THE THIRD GENERATION HEPATITIS B VACCINE (pre-S1/pre-S2/S)

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Abstract

Currently, second-generation hepatitis B vaccines are widely used. They are produced in biotechnological eukaryotic yeast-based systems and contain the S-protein domain of HBsAg particle in the complete absence of pre-S1 and pre-S2 domains. At the same time, these antigens were proved to significantly influence immunogenicity, which makes the development and use of third-generation vaccines containing all antigenic determinants a long-range objective. A randomized, double-blind clinical study was conducted to compare immunogenicity of second- and third-generation vaccines Engerix-B™ and Sci-B-Vac™, respectively. Healthy subjects of both sexes aged 18 to 45 years (n = 94) who are seronegative for HBsAg, HBsAb, HBcAb at screening and who previously had not received immunobiological agents for hepatitis B prophylaxis were included in the study. Group I (n = 47) received the second-generation vaccine Engerix-B™, Group II (n = 47) — the third-generation vaccine Sci-B-Vac™. Subjects received vaccines three times — on days 1, 28 and 180 of the study. HBsAb levels, rates of seroconversion (the proportion of subjects with HBsAb levels > 2.1 mIU/mL) and seroprotection (the proportion of subjects with HBsAb levels ≥ 10 mIU/mL) were assessed on days 28, 90, 180 and 210 of the study. Early seroconversion rate assessed on Day 28 was 76.60% in Group I and 93.88% in Group II (p < 0.05); seroprotection rate was 51.06 and 61.22%, respectively. These differences in the proportion of subjects who achieved seroconversion on Day 28 may indicate a faster immunological response to Sci-B-Vac™ vaccine. Statistically significant differences between the level of antibodies on days 90 and 180 (p < 0.05) were observed when analyzing the average values of HBsAb concentration in Groups I and II. The concentration of HBsAb on Day 90 was 378.68±60.95 mIU/mL in Group I, and 618.31±58.34 mIU/mL in Group II. On Day 180, the concentration of HBsAb reached 441.34±63.83 mIU/mL in Group I, and 757.72±55.14 mIU/mL in Group II. The significance of dependence of antibody level on sex, age and body weight was analyzed. It was revealed that the age of a vaccinated subject affects antibody level after administration of Engerix-B™ (p < 0.05). The results obtained suggest that there is a rapid and strong immune response to the third-generation vaccine Sci-B-Vac™. This may indicate advantage of the vaccine containing all three recombinant proteins of hepatitis B virus envelope, which, in turn, can play a key role in clinical practice for urgent prophylaxis of hepatitis B, as well as for treatment of immunocompromised conditions.

About the authors

E. V. Esaulenko

St. Petersburg State Pediatric Medical University

Author for correspondence.
Email: infection-gpmu@mail.ru

Elena V. Esaulenko - PhD, MD (Medicine), Professor, Head of Adult Infection Diseases and Epidemiology Department

194100, St. Petersburg, Litovskaya str., 2, Phone: +7 (812) 274-90-65

Russian Federation

A. A. Sukhoruk

St. Petersburg State Pediatric Medical University

Email: fake@neicon.ru

PhD (Medicine), Professor Assistant of Adult Infection Diseases and Epidemiology Department

Russian Federation

K. A. Zakharov

St. Petersburg State Pediatric Medical University

Email: fake@neicon.ru

Postgraduate Student at Adult Infection Diseases and Epidemiology Department

Russian Federation

A. A. Yakovlev

Clinical Infection Hospital named after S.P. Botkin

Email: fake@neicon.ru

PhD, MD (Medicine), Professor, Head of Infection Diseases, Epidemiology, Dermatology and Venerology Department St.PSU; Chief Physician at CIH named after S.P. Botkin

Russian Federation

References

  1. Вирусные гепатиты в Российской Федерации. Аналитический обзор. 10 выпуск. Под ред. В.И. Покровского, А.А. Тотоляна. СПб: ФБУН НИИЭМ имени Пастера, 2016. 152 с.
  2. Государственный реестр лекарственных средств Министерства здравоохранения Российской Федерации. URL: http://grls.rosminzdrav.ru/GRLS.aspx (19.02.2018)
  3. Елагин Р.И. Итоги и перспективы использования вакцины «Энджерикс В» для профилактики инфекции вирусом гепатита B // Consilium Medicum. 2001. № 8.
  4. О национальном календаре профилактических прививок и календаре профилактических прививок по эпидемическим показаниям: приказ Министерства здравоохранения Российской Федерации № 229 от 27.06.2001 г. URL: http://www.infectology.ru/forall/pricaz3.aspx (19.02.2018)
  5. Об утверждении санитарно-эпидемиологических правил СП 3.1.1.2341-08. Профилактика вирусного гепатита В: постановление Главного государственного санитарного врача Российской Федерации № 14 от 28.02.2008 г. Российская газета, 2008, № 4631 (0). URL: https://rg.ru/2008/04/05/gepatit-pravila-dok.html (19.02.2018)
  6. Cassidy W.M., Watson B., Ioli V.A., Williams K., Bird S., West D.J. A randomized trial of alternative two- and three-dose hepatitis B vaccination regimens in adolescents: antibody responses, safety, and immunologic memory. Pediatrics, 2001, vol. 107, no. 4, pp. 626–631.
  7. Diminsky D., Moav N., Gorecki M., Barenholz Y. Physical, chemical and immunological stability of CHO-derived hepatitis B surface antigen (HBsAg) particles. Vaccine, 1999, vol. 18, no. 1–2, pp. 3–17.
  8. Diminsky D., Schirmbeck R., Reimann J., Barenholz Y. Comparison between HBsAg particles derived from mammalian cells (CHO) and yeast cells (Hansenula polymorpha): composition, structure and immunogenicity. Vaccine, 1997, vol. 15, no. 6–7, pp. 637–647.
  9. Hauser P., Voet P., Simoen E., Thomas H.C., Petre J., De Wilde M., Stephenne J. Immunological properties of recombinant HBsAg produced in yeast. Postgrad. Med. J., 1987, vol. 63, suppl. 2, pp. 83–91.
  10. Heerman K.H., Goldmann U., Schwartz W., Seyffarth T., Baumgarten H., Gerlich W.H. Large surface proteins of hepatitis B virus containing the pre-S sequence. J. Virol., 1984, vol. 52, no. 2, pp. 396–402.
  11. Hepatitis B vaccine (rDNA). European Pharmacopoeia 7.0, 01/2008:1056. URL: http://www.fptl.ru/biblioteka/farmacop/EP-7.0-2.pdf (19.02.2018)
  12. Hourvitz A., Mosseri R., Solomon A., Yehezkelli Y., Atsmon J., Danon Y.L., Koren R., Shouval D. Reactogenicity and immunogenicity of a new recombinant hepatitis B vaccine containing Pre S antigens: a preliminary report. J. Viral. Hepat., 1996, vol. 3, no. 1, pp. 37–42.
  13. Immunisation policy. Global programme for vaccines and immunization. Expanded programme on immunization. World Health Organization. Geneva, Switzerland, 1995, 63 p. URL: http://apps.who.int/iris/bitstream/10665/63114/1/WHO_EPI_GEN_95.03_Rev.1.pdf (19.02.2018)
  14. Karpuch J., Scapa E., Eshchar J., Waron M., Bar-Shany S., Shwartz T. Vaccination against hepatitis B in a general hospital in Israel: antibody level before vaccination and immunogenicity of vaccine. Isr. J. Med. Sci., 1993, vol. 29, no. 8, pp. 449–452.
  15. Klinkert M.Q., Theilmann L., Pfaff E., Schaller H. Pre-S1 antigens and antibodies early in the course of acute hepatitis B virus infection. J. Virol., 1986, vol. 58, no. 2, pp. 522–525.
  16. London W.T., Drew J.S., Lustbader E.D., Werner B.G., Blumberg B.S. Host responses to hepatitis B infection in patients in a chronic hemodialysis unit. Kidney Int., 1977, vol. 12, iss. 1, pp. 51–58. doi: 10.1038/ki.1977.78
  17. Marsano L.S., West D.J., Chan I., Hesley T.M., Cox J., Hackworth V., Greenberg R.N. A two-dose hepatitis B vaccine regimen: proof of priming and memory responses in young adults. Vaccine, 1998, vol. 16, no. 6, pp. 624–629.
  18. Michel M.L., Pontisso P., Sobczak E., Malpiece Y., Streeck R.E., Tiollais P. Synthesis in animal cells of hepatitis B surface antigen particles carrying a receptor for polymerized human serum albumin. Proc. Natl. Acad. Sci. USA, 1984, vol. 81, no. 24, pp. 7708–7712.
  19. Milich D.R., Thornton G.B., Neurath A.R., Kent S.B., Michel M.L., Tiollais P., Chisari F.V. Enhanced immunogenicity of the pre-S region of hepatitis B surface antigen. Science, 1985, vol. 228, no. 4704, pp. 1195–1199.
  20. Neurath A.R., Kent S.B.H. The pre-S region of hepadnavirus envelope proteins. Adv. Virus. Res., 1988, vol. 34, pp. 65–142. doi: 10.1016/S0065-3527(08)60516-3
  21. Petit M.A., Maillard P., Capel F., Pillot J. Immunochemical structure of the hepatitis B surface antigen vaccine-II. Analysis of antibody responses in human sera against the envelope proteins. Mol. Immunol., 1986, vol. 23, no. 5, pp. 511–523.
  22. Raz R., Dagan R., Gallil A., Brill G., Kassis I., Koren R. Safety and immunogenicity of a novel mammalian cell-derived recombinant hepatitis B vaccine containing Pre-S1 and Pre-S2 antigens in children. Vaccine, 1996, vol. 14, no. 3, pp. 207–211.
  23. Raz R., Koren R., Bass D. Safety and immunogenicity of a new mammalian cell-derived recombinant hepatitis B vaccine containing Pre-S1 and Pre-S2 antigens in adults. Isr. Med. Assoc. J., 2001, vol. 3, no. 5, pp. 328–332.
  24. Recommendations to assure the quality, safety and efficacy of recombinant hepatitis B vaccines. Adopted by the 61st meeting of the WHO Expert Committee on Biological Standardization, 18 to 22 October 2010. URL: http://www.who.int/biologicals/HEP_B_Recomm_after_ECBS_endorsment_final.pdf (19.02.2018)
  25. Ribot S. Duration of hepatitis B surface antigenemia (HBsAg) in hemodialysis patients. Arch. Intern. Med., 1979, vol. 139, no. 2, pp. 178–180.
  26. Shapira M.Y., Zeira E., Adler R., Shouval D. Rapid seroprotection against hepatitis B following the first dose of Pre-S1/Pre-S2/S vaccine. J. Hepatol., 2001, vol. 34, no. 1, pp. 123–127.
  27. Shouval D., Ilan Y., Hourvitz A., Mosseri R., Solomon A., Zychowicz C., Gornicki J., Czubkowska I., Madalinski K., Burczynska B., Adler R., Gorecki M., Koren R. Immunogenicity of a mammalian cell-derived recombinant hepatitis B vaccine containing pre S2 and Pre S1 antigens: a preliminary report. Viral Hepatitis and Liver Disease. Eds. Nishioka K., Suzuki H., Mishiro S., Oda T. Tokyo: Springer Verlag, 1993, 543–546. doi: 10.1007/978-4-431-68255-4_142
  28. Szmuness W., Stevens C.E., Harley E.J., Zang E.A., Oleszko W.R., William D.C., Sadovsky R., Morrison J.M., Kellner A. Hepatitis B vaccine: demonstration of efficacy in a controlled clinical trial in a high-risk population in the United States. N. Engl. J. Med., 1980, vol. 303, no. 15, pp. 833–841.
  29. Szmuness W., Stevens C.E., Zang E.A., Harley E.J., Kellner A. A controlled clinical trial of the efficacy of the hepatitis B vaccine (Heptavax B): a final report. Hepatology, 1981, vol. 1, no. 5, pp. 377–385.
  30. Van Damme P., Van Herck K. A review of the long-term protection after hepatitis A and B vaccination. Trav. Med. Infect. Dis., 2007, vol. 5, no. 2, pp. 79–84. doi: 10.1016/j.tmaid.2006.04.004
  31. World Health Organization. Prequalified Vaccines. Geneva, Switzerland. URL: https://extranet.who.int/gavi/PQ_Web/ (19.02.2018)
  32. Yap I., Guan R., Chan S.H. Comparison of immunogenicity of a pre-S containing HBV vaccine with non-pre-S containing vaccines (Abstract 272). Viral hepatitis and liver disease: proceedings of the International Symposium on Viral Hepatitis and Liver Disease (8th Triennial Congress). Eds. Nishioka K., Suzuki H., Mishiro S., Oda T. Tokyo: Springer Verlag, 1993, p. 86.
  33. Yap I., Guan R., Chan S.H. Recombinant DNA hepatitis B vaccine containing Pre-S components of the HBV coat protein-a preliminary study on immunogenicity. Vaccine, 1992, vol. 10, no 7, pp. 439–432.
  34. Yap I., Guan R., Chan S.H. Study on the comparative immunogenicity of a recombinant DNA hepatitis B vaccine containing pre-S components of the HBV coat protein with non pre-S containing vaccines. J. Gastroenterol. Hepatol., 1995, vol. 10, iss. 1, pp. 51–55. doi: 10.1111/j.1440-1746.1995.tb01047.x
  35. Yerushalmi B., Raz R., Blondheim O., Shumov E., Koren R., Dagan R. Safety and immunogenicity of a novel mammalian cellderived recombinant hepatitis B vaccine containing Pre-S1 and Pre-S2 antigens in neonates. Pediatr. Infect. Dis., 1997, vol. 16, no. 6, pp. 587–592.

Copyright (c) 2018 Esaulenko E.V., Sukhoruk A.A., Zakharov K.A., Yakovlev A.A.

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