Recognition of Core‐ and Polymerase‐derived immunogenic peptides included in novel therapeutic vaccine by T cells from Chinese chronic hepatitis B patients

Abstract

SummaryChronic hepatitis B (CHB) is one of the major public health challenges in the world.Due to a strong interplay between specific T-cell immunity and elimination of hepatitis B virus (HBV), efforts to develop novel immunotherapeutics are gaining attention. TG1050, a novel immunotherapy, has shown efficacy in an animal study. To support the clinical development of TG1050 in China, specific immunity to the fusion antigens of TG1050 was assessed in Chinese patients. One hundred and thirty subjects were divided into three groups as CHB patients, HBV spontaneous resolvers, and CHB patients with HBsAg loss after antiviral treatment. HBV-specific T-cell responses to pools of HBV Core or Polymerase genotype D peptides included in TG1050 were evaluated. HBV Core-or Polymerase-specific cells were detected in peripheral blood mononuclear cells (PBMCs) from the different cohorts. The frequencies and intensities of HBV Core-specific immune responses were significantly lower in CHB patients than in HBsAg loss subjects. In CHB patients, a dominant pool derived from Polymerase (Pol1) was the most immunogenic. CHB patients with low viral loads (<10 6 IU/mL) were more likely to have a positive response specific to the Core peptide pool. Overall, genotype D-derived peptides included in TG1050 could raise broad and functional T-cell responses in PBMCs from Chinese CHB patients infected with genotype B/C isolates. Core-specific immunogenic domains appeared as "hot spots" with the capacity to differentiate between CHB vs HBsAg loss subjects. These observations support the extended application and associated immune monitoring of TG1050 in China. K E Y W O R D SCore and Polymerase, HBV, HBV genotype, immune response, TG1050This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

What will it take to cure hepatitis B?

“… 83 , 84 New approaches to therapeutic vaccines include the use of viral vectors, antigens from HBV core or polymerase regions, and combination with immune checkpoint inhibitors. 83 – 88 A phase 1b/2a trial of Chimpanzee adenoviral and modified vaccinia Ankara viral vectors encoding multiple HBV antigens (ChAdOx1-HBV/MVA-HBV) used in a prime-boost strategy in virally suppressed patients showed that the addition of low-dose nivolumab (programmed death receptor-1 inhibitor) resulted in greater HBsAg decline (mean 1 log 10 at 6 months) and 1 patient lost HBsAg lasting 8 months after the last dose. 89 …”