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

Abstract

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 ug HBsAg and 100 ug 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. How to cite this article: Fernandez G, Sanchez AL, Jerez E, Anillo LE, Freyre F, Aguiar JA, Leon Y, Cinza Z, Diaz PA, Figueroa N, Muzio V, Nieto GG, Lobaina Y, Aguilar A, Penton E, Aguilar JC. 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.

New Approaches to the Treatment of Chronic Hepatitis B

“…Similarly, in a phase I trial in Cuba, six CHB patients unresponsive to Peg-IFN treatment, received the vaccine as described and after a five-year follow-up, HBeAg loss was achieved in three HBeAg positive patients, in two cases with seroconversion to anti-HBe. An undetectable viral load was present in 5/6 and seroconversion to anti-HBs in two patients [ 105 ].…”

From hepatitis A to E: A critical review of viral hepatitis

“…Special interest has been directed to therapeutic vaccines to achieve functional HBV cure. Even though different therapeutic vaccines have been studied, the HeberNavac HBsAg-HBcAg is the only vaccine that has shown significant HBeAg seroconversion rates compared to PEG-interferon in a randomized phase III trial[ 83 ]. Although promising, immunotherapy remains a territory to be explored and similar to HCV the goal of viral eradication remains at the core of research efforts.…”

Novel Antivirals in Clinical Development for Chronic Hepatitis B Infection

“…ABX-203 (HeberNasvac), a yeast-based vaccine that comprises HBsAg and HBcAg virus-like particles, was studied in phase 1–3 clinical trials. It led to HBsAg seroclearance in two out of six CHB patients who had prior PEG-IFN treatment and were given ABX-203 intranasally every 2 weeks for up to 5 years [ 79 ]. TG-1050, an adenovirus 5-based vaccine that expresses HBV polymerase and domains of core and HBsAg, was shown to induce specific IFNγ-producing T cells and led to minor reductions of HBsAg and significant reductions in HBcrAg in NA-treated CHB patients [ 80 ].…”