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

Abstract

SummaryThere are estimated to be 350 million chronic carriers of hepatitis B infection worldwide. Patients with chronic hepatitis B are at risk of liver cirrhosis with associated mortality because of hepatocellular carcinoma and other complications. An important goal, therefore, is the development of an effective therapeutic vaccine against chronic hepatitis B virus (HBV). A major barrier to the development of such a vaccine is the impaired immune response to HBV antigens observed in the T cells of affected patients. One strategy to overcome these barriers is to activate mucosal T cells through the use of nasal vaccination because this may overcome the systemic immune downregulation that results from HBV infection. In addition, it may be beneficial to present additional HBV epitopes beyond those contained in the traditional hepatitis B surface antigen (HbsAg) vaccine, for example, by using the hepatitis B core antigen (HBcAg). This is advantageous because HBcAg has a unique ability to act as a potent Th1 adjuvant to HbsAg, while also serving as an immunogenic target. In this study we describe the effect of coadministration of HBsAg and HBcAg as part of a strategy to develop a more potent and effective HBV therapeutic vaccine.

The Adoptive Transfer of HBsAG-specific Splenocytes from Balb/c Congenic Donors into HBsAg Transgenic Mice is not associated to Histographological Damage

“…Fifteen days after receiving the booster dose the donor animals and the animals from the control group were VDFUL¿FHG DQG WKH VSOHHQV ZHUH SURFHVVHG 7RWDO VSOHHQ FHOOV ZHUH SXUL¿HG DV SUHYLRXVO\ UHSRUWHG 13 Vials containing 30 × 10 6 cells in 100 Pl of PBS 1× were obtained for individual transfer. Two of this vials received a restimulation previous to the transfer.…”

“…13 %ULHÀ\ WKH VROLG SKDVH ZDV sensitized with HBsAg or HBcAg at 5Pg/ml of each protein, then the plates were blocked using 2% skim milk and after washing the sera samples applied at different dilutions, then it was incubated with the anti-mouse IgG peroxidase EJOHG conjugate (SIGMA, USA). Finally, the plates were washed 5-fold and the O-phenylenediamine/hydrogen peroxide substrate solution was applied.…”

Research progress of therapeutic vaccines for treating chronic hepatitis B

“…In particular, HBcAg acts as a Th1 adjuvant and has a synergistic effect on antibody production and cellular responses when co-administered with HBsAg. 55,58,59 In the Phase I clinical trial, 19 healthy male adults were enrolled to evaluated the safety profile and immunogenicity of NASVAC for nasal administration. The participants received either NASVAC (50 mg HBsAg and 50 mg HBcAg) or placebo (0.9% physiologic saline) on day 0, 7, 15, 30, and 60, respectively.…”

ABX203, a novel therapeutic vaccine for chronic hepatitis B patients

“…Immunogenicity of ABX203 has been extensively studied in normal and transgenic mice [6,7,[20][21][22][23]. In Balb/c mice, immunogenicity of this combination formulation at different doses and antigen ratios was explored using parenteral and mucosal immunization routes [6,7,20,24].…”

“…The vaccine is based on a combination of the HBsAg and the HBV nucleocapsid (HBcAg) antigens and is simultaneously administered by the intranasal and subcutaneous routes [6,7]. ABX203 has been studied in phase I, phase II and phase III clinical trials with promising results [8][9][10].…”