ABX203, a novel therapeutic vaccine for chronic hepatitis B patients

Cover Page

Cite item


Despite the existence of effective prophylactic vaccines, chronic hepatitis B remains a major public health problem, with more than 350 million people infected   worldwide.  Chronic  infection   increases the  risk of serious  liver diseases  such  as cirrhosis and  hepatocellular carcinoma.  Available therapies for chronic  hepatitis  B  have  limited  efficacy and require  long-term   continuous  treatments;  that  is why the  development of therapeutic vaccines has been  investigated as  promising  approach.  In this sense, a novel  vaccine  formulation  called ABX203 (HeberNasvac), based  on  the  combination of the hepatitis B virus nucleocapsid and surface antigens, was developed. ABX203 has been studied in phase I, phase II and phase III clinical trial in treatment-naïve chronically infected  patients  in Bangladesh  and  in healthy  volunteers  in Cuba with promising  results. In the present work we reviewed the main preclinical and   clinical  results  of  ABX203 development. Altogether, the data demonstrates safety and immunogenicity of ABX203 vaccine and support  its use as a novel and competitive treatment alternative for chronic hepatitis B. The vaccine has been granted marketing authorization in Cuba.

About the authors

Y. Lobaina Mato

Center for Genetic Engineering and Biotechnology, Havana

Email: fake@neicon.ru
Lobaina Mato Yadira – PhD, Researcher, Hepatitis B therapeutic vaccine Project, Vaccine Department, Biomedical Research Unit Cuba

J.C. Aguilar Rubido

Center for Genetic Engineering and Biotechnology, Havana

Email: fake@neicon.ru
Aguilar Rubido Julio Cesar – PhD, Senior Researcher, Head of Hepatitis B therapeutic vaccine Project, Vaccine Department, Biomedical Research Unit Cuba

G.E. Guillén Nieto

Center for Genetic Engineering and Biotechnology, Havana

Author for correspondence.
Email: gerardo.guillen@cigb.edu.cu

Guillen Nieto Gerardo Enrique – PhD, Member of the Cuban Academy of Science, Senior Researcher, Biomedical Research Director.

31 Avenue, P.O. Box 6162, Havana 6, 10 600, Cuba. Tel: (53-7) 250 44 95. E-mail: gerardo.guillen@cigb.edu.cu



  1. World Health Organization. Global policy report on the prevention and control of viral hepatitis in WHO Member States. Geneva: WHO Press; 2013. 208 p. Available from: http://apps.who.int/iris/bitstre am/10665/85397/1/9789241564632_eng.pdf.
  2. Gish RG, Given BD, Lai CL, Locarnini SA, Lau JYN, Lewis DL, Schluep T. Chronic hepatitis B: Virology, natural history, current management and a glimpse at future opportunities Antiviral Res. 2015;121:47–58. doi: 10.1016/j.antiviral.2015.06.008.
  3. Vandepapeliere P, Lau GK, Leroux-Roels G, Horsmans Y, Gane E, Tawandee T, bin Merican MI, Win KM, Trepo C, Cooksley G, Wettendorff M, Ferrari C; Therapeutic HBV Vaccine Group of Investigators. Therapeutic vaccination of chronic hepatitis B patients with virus suppression by antiviral therapy: A randomized, controlled study of co-administration of HBsAg/AS02 candidate vaccine and lamivudine. Vaccine. 2007;25(51):8585–97. doi: 10.1016/j.vaccine.2007.09.072.
  4. Aguilar JC, Lobaina Y. Immunotherapy for chronic hepatitis B using HBsAg based vaccine formulations: from preventive commercial vaccines to therapeutic approach. Euroasian J Hepato-Gastroenterol. 2014;4(2):53–8. doi: 10.5005/jp-journals-10018-1109.
  5. Michel ML, Deng Q, Mancini-Bourgine M. Therapeutic vaccines and immune-based therapies for the treatment of chronic hepatitis B: Perspectives and challenges. J Hepatol. 2011;54(6):1286–96. doi: 10.1016/j.jhep.2010.12.031.
  6. Aguilar JC, Lobaina Y, Muzio V, Garcia D, Penton E, Iglesias E, Pichardo D, Urquiza D, Rodriguez D, Silva D, Petrovsky N, Guillen G. Development of a nasal vaccine for chronic hepatitis B infection that uses the ability of hepatitis B core antigen to stimulate a strong Th1 response against hepatitis B surface antigen. Immunol Cell Biol. 2004;82(5):539–46. doi: 10.1111/j.0818-9641.2004.01278.x.
  7. Lobaina Y, Trujillo H, Garcia D, Gambe A, Chacón Y, Blanco A, Aguilar JC. The effect of the parenteral route of administration on the immune response to simultaneous nasal – parenteral immunizations using a new HBV therapeutic vaccine candidate. Viral Immunol. 2010;23(5):521–9. doi: 10.1089/vim.2010.0024.
  8. Betancourt AA, Delgado CA, Estévez ZC, Martínez JC, Ríos GV, Aureoles-Roselló SR, Zaldívar RA, Guzmán MA, Baile NF, Reyes PA, Ruano LO, Fernández AC, Lobaina-Matos Y, Fernández AD, Madrazo AI, Martínez MI, Baños ML, Alvarez NP, Baldo MD, Mestre RE, Pérez MV, Martínez ME, Escobar DA, Guanche MJ, Cáceres LM, Betancourt RS, Rando EH, Nieto GE, González VL, Rubido JC. Phase I clinical trial in healthy adults of a nasal vaccine candidate containing recombinant hepatitis B surface and core antigens. Int J Infect Dis. 2007;11(5):394–401. doi: 10.1016/j.ijid.2006.09.010.
  9. Al-Mahtab M, Akbar SM, Aguilar JC, Uddin H, Khan SI, Rahman S. Therapeutic potential of a combined hepatitis B virus surface and core antigen vaccine in patients with chronic hepatitis B. Hepatol Int. 2013;7(4):981–9. doi: 10.1007/s12072-013-9486-4.
  10. Akbar SM, Al-Mahtab M, Rahman S, Aguilar JC, Hiasa Y, Mishiro S. A phase III clinical trial with a therapeutic vaccine containing both HBsAg and HBcAg administered via both mucosal and parenteral routes in patients with chronic hepatitis B. Hepatology. 2013;58(S1):647A–705A. doi: 10.1002/hep.26727.
  11. Lau GK, Suri D, Liang R, Rigopoulou EI, Thomas MG, Mullerova I, Nanji A, Yuen ST, Williams R, Naoumov NV. Resolution of chronic hepatitis B and anti-HBs seroconversion in humans by adoptive transfer of immunity to hepatitis B core antigen. Gastroenterology. 2002;122(3):614–24. doi: http://dx.doi. org/10.1053/gast.2002.31887.
  12. Riedl P, Stober D, Oehninger C, Melber K, Reimann J, Schirmbeck R. Priming Th1 Immunity to Viral Core Particles Is Facilitated by Trace Amounts of RNA Bound to Its Arginine-Rich Domain. J Immunol. 2002;168(10):4951–9. doi: 10.4049/jimmunol.168.10.4951.
  13. Bertoletti A, Naoumov NV. Translation of immunological knowledge into better treatments of chronic Hepatitis B. J Hepatol. 2003;39(1):115–24. doi: 10.1016/S0168-8278(03)00126-0.
  14. Bertoletti A, Ferrari C. Innate and adaptive immune responses in chronic hepatitis B virus infections: towards restoration of immune control of viral infection. Gut. 2012;61(12):1754–64. doi: 10.1136/gutjnl-2011-301073.
  15. Davis SS. Nasal vaccines. Adv Drug Deliv Rev.;51(1–3):21–42. Available from: http://dx.doi.org/10.1016/S0169-409X(01)00162-4.
  16. Liaw YF, Chu CM. Hepatitis B virus infection. Lancet. 2009;373(9663):582–92. doi: 10.1016/S0140-6736(09)60207-5.
  17. Holmgren J, Czerkinsky C. Mucosal immunity and vaccines. Nat Med. 2005;11(4 Suppl):S45–53. doi: 10.1038/nm1213.
  18. Vajdy M, Singh M, Kazzaz J, Soenawan E, Ugozzoli M, Zhou F, Srivastava I, Bin Q, Barnett S, Donnelly J, Luciw P, Adamson L, Montefiori D, O'Hagan DT. Mucosal and systemic anti-HIV responses in rhesus macaques following combinations of intranasal and parenteral immunizations. AIDS Res Hum Retroviruses. 2004;20(11):1269–81. doi: 10.1089/aid.2004.20.1269.
  19. Makitalo B, Lundholm P, Hinkula J, Nilsson C, Karlen K, Morner A. Enhanced cellular immunity and systemic control of SHIV infection by combined parenteral and mucosal administration of a DNA prime MVA boost vaccine regimen. J Gen Virol. 2004;85(Pt 8):2407–19. doi: 10.1099/vir.0.79869-0.
  20. Lobaina Y, Palenzuela D, Pichardo D, Muzio V, Guillen G, Aguilar JC. Immunological characterization of two hepatitis B core antigen variants and their immunoenhancing effect on co-delivered hepatitis B surface antigen. Mol Immunol. 2005;42(3):289–94. doi: 10.1016/j.molimm.2004.09.005.
  21. Trujillo H, Blanco A, Garcia D, Freyre F, Aguiar J, Lobaina Y, Aguilar JC. Optimization of a therapeutic vaccine candidate by studying routes, immunizations schedules and antigen doses in HBsAg-positive transgenic mice. Euroasian J Hepato-Gastroenterol. 2014;4(2):70–8. doi: 10.5005/jp-journals-10018-1105.
  22. Lobaina Y, García D, Blanco A, Hernández D, Trujillo H, Freyre F, Merino N, Suarez J, Ancizar J, Martinez L, Aguilar JC. The adoptive transfer of HBsAg-specific splenocytes from BALB/c congenic donors into HBsAg transgenic mice is not associated to histopathological damage. Euroasian J Hepato-Gastroenterol. 2013;3(2):97–102. doi: 10.5005/jp-journals-10018-1074.
  23. Bourgine M, Dion S, Godon O, Guillen G, Michel ML, Aguilar JC. Optimization of immune responses induced by therapeutic vaccination with cross-reactive antigens in a humanized hepatitis B surface antigen transgenic mouse model. Virology. 2012;430(1):10–9. doi: 10.1016/j.virol.2012.04.007.
  24. Lobaina Y, Garcia D, Rodriguez D, La OY, Aguilar JC. Characterization of the immune response generated in mice by intramuscular administration of a formulation containing the nucleocapsid and surface antigen of hepatitis B. Biotecnologia Aplicada. 2010;27(3):211–5.
  25. Maini MK, Boni C, Lee CK, Larrubia JR, Reignat S, Ogg GS, King AS, Herberg J, Gilson R, Alisa A, Williams R, Vergani D, Naoumov NV, Ferrari C, Bertoletti A. The role of virus-specific CD8 (+) cells in liver damage and viral control during persistent hepatitis B virus infection. J Exp Med. 2000;191(8):1269–80. doi: 10.1084/jem.191.8.1269.
  26. Yang PL, Althage A, Chung J, Maier H, Wieland S, Isogawa M, Chisari FV. Immune effectors required for hepatitis B virus clearance. Proc Natl Acad Sci U S A. 2010;107(2):798–802. doi: 10.1073/pnas.0913498107.
  27. Castro FO, Perez A, Aguilar A, de la Riva G, Martinez R, de la Fuente J, Herrera L. Expresión del gen del antigeno de superficie del virus de la hepatitis B en ratones transgénicos. Interferon y Biotecnología. 1989;6(3):251–7 (in Spanish).
  28. Freyre F, Blanco A, Trujillo H, Hernandez D, Garcia D, Alba J, Lopez M, Merino N, Lobaina Y, Aguilar JC. Dynamic of immune response induced in hepatitis B surface antigen-transgenic mice immunized with a novel therapeutic formulation. Euroasian J Hepato-Gastroenterol. 2016;6(1):25–30. doi: 10.5005/jp-journals-10018-1161.
  29. Schirmbeck R, Wild J, Stober D, Blum HE, Chisari FV, Geissler M, Reimann J. Ongoing murine T1 or T2 immune responses to the hepatitis B surface antigen are excluded from the liver that expresses transgene-encoded hepatitis B surface antigen. J. Immunol. 2000;164(8):4235–43. doi: 10.1111/j.1348-0421.2003.tb03370.x.
  30. Shimizu Y, Guidotti LG, Fowler P, Chisari FV. Dendritic cell immunization breaks cytotoxic T lymphocyte tolerance in hepatitis B virus transgenic mice. J. Immunol. 1998;161(9):4520–9.
  31. Mancini-Bourgine M, Guillen G, Michel ML, Aguilar JC. Impact of the immunogen nature on the immune response against the major HBV antigens in an HBsAg and HLA-humanized transgenic mouse model. Euroasian J Hepato-Gastroenterol. 2014;4(1):36–44. doi: 10.5005/jp-journals-10018-1094.
  32. Downs RW, Bell NH, Ettinger MP, Walsh BW, Favus MJ, Mako B, Wang L, Smith ME, Gormley GJ, Melton ME. Comparison of Alendronate and intranasal Calcitonin for treatment of osteoporosis in postmenopausal women. J Clin Endocrinol Metab. 2000;85(5):1783–8. doi: 10.1210/jcem.85.5.6606.
  33. Nichol KL, Mendelman PM, Mallon KP, Jackson LA, Gorse GJ, Belshe RB, Glezen WP, Wittes J. Effectiveness of live, attenuated intranasal influenza virus vaccine in healthy, working adults: a randomized controlled trial. JAMA. 1999;282(2):137–44. doi: 10.1001/jama.282.2.137.

Copyright (c) 2016 Lobaina Mato Y., Aguilar Rubido J., Guillén Nieto G.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies