Euroasian journal of hepato-gastroenterology

Register      Login

VOLUME 8 , ISSUE 2 ( July-December, 2018 ) > List of Articles


Five-year Follow-up of Chronic Hepatitis B Patients Immunized by Nasal Route with the Therapeutic Vaccine HeberNasvac

Julio Cesar Aguilar, Yamila León, Yadira Lobaina, Freya Freyre, Guillermo Fernández, Ana L Sanchez, Everardo Jerez, Luis E Anillo, Jorge A Aguiar, Zurina Cinza, Pablo A Diaz, Nelvis Figueroa, Verena Muzio, Gerardo G Nieto, Arístides Aguilar, Eduardo Penton

Keywords : Chronic hepatitis B, HeberNasvac, Therapeutic vaccine

Citation Information : Aguilar JC, León Y, Lobaina Y, Freyre F, Fernández G, Sanchez AL, Jerez E, Anillo LE, Aguiar JA, Cinza Z, Diaz PA, Figueroa N, Muzio V, Nieto GG, Aguilar A, Penton E. Five-year Follow-up of Chronic Hepatitis B Patients Immunized by Nasal Route with the Therapeutic Vaccine HeberNasvac. Euroasian J Hepatogastroenterol 2018; 8 (2):133-139.

DOI: 10.5005/jp-journals-10018-1279

License: CC BY-NC 4.0

Published Online: 01-01-2019

Copyright Statement:  Copyright © 2018; The Author(s).


A novel therapeutic vaccine for chronic hepatitis B (CHB) treatment comprising the recombinant hepatitis B surface (HBsAg) and nucleocapsid (HBcAg) antigens has been developed. Preclinical and clinical trials (CT) evidenced safety and immunogenicity in animal models as well as in phases I, II, and III clinical trials. A phase I CT has conducted in Cuba in 6 CHB patients refractory or incomplete responders to α-IFN. Patients were immunized ten times every two weeks via. nasal spray, with 100 μg HBsAg and 100 μg HBcAg. Clinical efficacy was monitored by assessing the levels of hepatitis B virus deoxyribonucleic acid (HBV DNA), alanine aminotransferase (ALT), HBeAg, and anti-HBeAg seroconversion as well as by qualitative/ quantitative HBsAg serology during this period. After a 5 year follow-up, HBeAg loss was verified in the three HBeAg (+) patients, in two cases with seroconversion to anti-HBeAg. A reduction to undetectable viral load was observed in 5 out of 6 patients, and in two cases HBsAg seroconversion was also detected. ALT increases above the 2X upper limit of normal (ULN) were only detected in HBeAg (+) patients and associated with HBe antigen loss. All patients had stiffness levels below 7.8 KPa by Fibroscan assessment at the end of this period. Although only a few patients were enrolled in this study, it seems that HeberNasvac may maintain some of the therapeutic effects for a prolonged period.

PDF Share
  1. Global Hepatitis Report 2017. Geneva: World Health Organization; 2017.
  2. Block TM, Gish R, Guo H, Mehta A, Cuconati A, Thomas London W, et al. Chronic hepatitis B: what should be the goal for new therapies? Antiviral Res. 2013;98(1):27-34.
  3. Michel ML, Deng Q, Mancini-Bourgine M. Therapeutic vaccines and immune-based therapies for the treatment of chronic hepatitis B: Perspectives and challenges. Journal of Hepatology 2011;54:1286-1292.
  4. Aguilar JC, Lobaina Y, Muzio V, Garcia D, Penton E, Iglesias E, et al. 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;82:539-546.
  5. 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. Molecular Immunology 2005;42:289.294.
  6. Lobaina Y, Trujillo H, Garcia D, Gambe A, Chacon 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 Immunology 2010;23(5):521-529.
  7. Lobaina Y, Garcia D, Blanco A, Hernandez D, Trujillo H, Freyre FM, et al. The adoptive transfer of HBsAg-specific splenocytes from Balb/c congenic donors into HBsAg transgenic mice is not associated to histopathological damage. Euroasian Journal of Hepato-Gastroenterology 2013;3(2):97-102.
  8. Aguilar A, Delgado CA, Cinza Z, Martinez JC, Rios GV, Aureoles-Rosello SR, et al. 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.
  9. Al-Mahtab M, Akbar SM, Aguilar JC, Uddin MH, Khan MS, 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):981-989.
  10. Akbar SM, Al- Mahtab M, Rahman S, Aguilar JC, Hiasa Y, Mishiro S. A phase III clinical trial with a therapeutic vaccine containingboth HBsAg and HBcAg administered via bothmucosal and parenteral routes in patients with chronic hepatitis B. Hepatology 2013;58:4.
  11. Al Mahtab M, Akbar SMF, Aguilar JC, Guillen G, Penton E, Tuero A, et al. Treatment of chronic hepatitis B naive patients with a therapeutic vaccine containing HBs and HBc antigens (a randomized, open and treatment controlled phase III clinical trial). PLoS One. 2018 Aug 22;13(8):e0201236.
  12. Mahtab MA Epidemiology of Viral Hepatitis and Liver Diseases in Bangladesh. Euroasian J Hepatogastroenterol. 2015 Jan-Jun;5(1):26-29.
  13. Mahtab MA, Chaudhury M, Uddin MH, Noor-E Alam SM, Rahim MA, Alam MA, et al. Cost Assessment of Hepatitis B Virus-related Hepatitis in Bangladesh. Euroasian J Hepatogastroenterol. 2016 Jul-Dec;6(2):163-166.
  14. Guillen G, Lobaina Y, Bourgine M, Michel ML, Freyre F, Aguilar JC. Pharmacological development of HeberNasvac, a novel therapeutic vaccine against chronic hepatitis B. Abstracts of the 26th Annual Conference of APASL, February 15.19, 2017, Shanghai, China. Hepatol Int. 2017; 11 (Suppl 1): S1.S1093.
  15. Hardy E, Martinez E, Diago D, Diaz R, Gonzalez D, Herrera L. Large-scale production of recombinant hepatitis B surface antigen from Pichia pastoris. J Biotechnol. 2000;77:157- 167.
  16. Aguilar JC, Lobaina Y, Muzio V, Garcia D, Penton E, Iglesias E, et al. 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- 546.
  17. Lobaina Y, Aguilar JC, Guillen G. ABX203, a novel therapeutic vaccine for chronic hepatitis B patients. Almanac of Clinical Medicine. 2016;44(6):713.718.
  18. Aguilar JC, Lobaina Y, Muzio V, Garcia D, Penton E, Iglesias E, et al. High Functional Stability of a Low-cost HBV DNA qPCR Primer Pair and Plasmid Standard Euroasian J of Hepato- Gastroenterology. 2016;6(1):1-6.
  19. Aguiar J, Rodriguez L, Leon Y, Freyre F, Silva JA, Montalvo MC, et al. Hepatitis B Virus DNA Quantification Using a Cost Effective and Simple Real Time PCR in Cuban Carriers. Journal of Infectious Diseases and Therapeutics. 2014;2:49-58.
  20. European Association for the Study of the Liver. Electronic address:; European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67(2):370-398.
  21. Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. American Association for the Study of Liver Diseases. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63(1):261-283.
  22. Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10(1):1-98.
  23. Sonneveld MJ, Zoutendijk R, Flink HJ, Zwang L, Hansen BE, Janssen HL. Close monitoring of hepatitis B surface antigen levels helps classify flares during peginterferon therapy and predicts treatment response. Clin Infect Dis. 2013;56(1):100- 105.
  24. Liaw YF. Hepatitis flares and hepatitis B e antigen seroconversion: implication in anti-hepatitis B virus therapy. J Gastroenterol Hepatol. 2003; 18(3):246-252.
  25. Flink HJ, Sprengers D, Hansen BE, van Zonneveld M, De Man RA, Schalm SW, Janssen HL. Flares in chronic hepatitis B patients induced by the host or the virus? Relation to treatment response during Peg-interferon ƒ¿-2b therapy. Gut. 2005 Nov 1;54(11):1604-1609.
  26. Papatheodoridis G, Vlachogiannakos I, Cholongitas E, Wursthorn K, Thomadakis C, Touloumi G, et al. Discontinuation of oral antivirals in chronic hepatitis B: A systematic review. Hepatology. 2016;63(5):1481-1492.
  27. Chunxiang F, Bike Z, Lijie Z, Hutin Y, Jie L, Jiang T, et al. Injection safety assessments in two Chinese provinces, 2001-2009: progress and remaining challenges. Int Health. 2012;4(4): 295-302.
  28. Xu DZ, Zhao K, Guo LM, Li LJ, Xie Q, Ren H, et al. A randomized controlled phase IIb trial of antigen-antibody immunogenic complex therapeutic vaccine in chronic hepatitis B patients. PLoS One. 2008;3(7):e2565.
  29. Fontaine H, Kahi S, Chazallon C, Bourgine M, Varaut A, Buffet C, et al. ANRS HB02 study group. Anti-HBV DNA vaccination does not prevent relapse after discontinuation of analogues in the treatment of chronic hepatitis B: a randomised trial. ANRS HB02 VAC-ADN. Gut. 2015;64(1):139-147.
  30. Vandepapeliere P, Lau GK, Leroux-Roels G, Horsmans Y, Gane E, Tawandee T, et al. 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): 8585-8597.
  31. Aguilar JC, Lobaina Y. Immunotherapy for Chronic Hepatitis B using HBsAg-based Vaccine Formulations: From Preventive Commercial Vaccines to Therapeutic Approach Julio Cesar Aguilar. Euroasian J Hepatogastroenterol. 2014 Jul- Dec;4(2):92-97
  32. Mf Akbar S, Al-Mahtab M, I Khan S. Nature of Host Immunity during Hepatitis B Virus Infection and designing Immune Therapy. Euroasian J Hepatogastroenterol. 2018 Jan- Jun;8(1):42-46.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.