Hepatitis & Liver Diseases

Biography

Biography: Julio Cesar Aguilar Rubido

Abstract

Chronic hepatitis B (CHB) infection constitutes a major cause of HCC, liver cirrhosis worldwide. HeberNasvac is a novel therapeutic vaccine based in the recombinant HBsAg and HBcAg. These proteins contain adjuvant and immunomodulatory properties that supported the clinical development of HeberNasvac. Materials & Methods: Four clinical trials evaluated the administration of HeberNasvac, three of them in CHB patients. Two studies were carried out in treatment-naïve patients and a third was conducted in non-responders to IFN- therapy. The viral load was monitored as main variable in all the studies involving CHB patients. Serological evaluations for HBe and HBsAg and their corresponding antibodies were also conducted. The transaminases, bilirubin and other liver and hematological markers were evaluated to assess product safety. Balb/c mice, rabbits and AAV HBV transfected/HLA double transgenic mice were used as models to evaluate the capacity of the nasal route of immunization to generate systemic and especially liver immune responses. Results: Clinical trials evidenced a significant reduction of the viral load to undetectable levels and under 10⁴ copies/mL, both at end of treatment and after 24/48 weeks follow-up evaluations, evidencing the sustained control of the virus. Liver function tests and hematological variables evidenced the safety of this product. Serological responses were higher to PegIFN treatment. Action mechanism studies related to the route of immunization evidenced the role of the nasal route of immunization in the induction of T cells at the target organ, the liver. Conclusions: The vaccination with HeberNasvac is effective and safe, supporting its use as therapy against CHB infection. The studies of immunogenicity in novel model of CHB infection evidenced the effect of the nasal route of immunization in the liver homing of effector T cells. These results suggest that HeberNasvac may contribute as a novel treatment for CHB.

Publications:

1: Lobaina Y, Hardtke S, Wedemeyer H, Aguilar JC, Schlaphoff V. In vitro stimulation with HBV therapeutic vaccine candidate Nasvac activates B and T cells from chronic hepatitis B patients and healthy donors. Mol Immunol. 2015 Feb; 63(2):320-7.

2: 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 Oct;7(4):981-9.

3: 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 Aug 15; 430(1):10-9.

4: Lobaina Y, Trujillo H, García D, Chacon Y, Aguilar JC. The effect of the parenteral route of administration on the immune response to simultaneous nasal and parenteral immunizations using a new HBV therapeutic vaccine candidate. Viral Immunol. 2010 Oct;23(5):521-9.

5: Loureiro CL, Aguilar JC, Aguiar J, Muzio V, Pentón E, et al. HBV genotypic variability in Cuba. PLoS One. 2015 Mar 5;10(3):e0118959.