HBV-specific T-cell response and viral evolution in a transmission pair with acute-persistent HBV infection

Background and aims In acute HBV infection, T-cell responses are strong and broad, but they become weak and dysfunctional in chronic infection. The timing and role of viral escape in this transition are unclear. We thus longitudinally analyzed viral evolution and HBV-specific T-cell responses in a transmission pair with acute-persistent infection in the recipient. Methods PBMC and serum samples from an HBV genotype D transmission pair were collected at eight time points over eight years. PBMCs were screened for responses to overlapping peptides covering the full HBV proteome during both acute and chronic phases, and autologous viral sequences were analyzed over time. Results The recipient of the transmission event developed an acute infection with a maximum ALT level of 556 U/L and a viral load of 45 million IU/mL, followed by chronic infection. HBeAg seroconversion occurred after 6 years. OLP screening revealed T-cell responses to 4 epitopes, whose viral sequences remained unchanged during the transition to chronic infection. After seroconversion, a total of 10 amino acid mutations were detected (4 in the core and 6 in the polymerase protein), including 2 within recognized core epitopes and 6 within predicted epitopes. Conclusion These findings are consistent with previous reports indicating that viral mutations occur more frequently in patients with HBeAg-negative chronic HBV infection than in those with HBeAg-positive infection, and indicate that viral escape temporally indeed coincides with HBe seroconversion. The contribution of viral escape to the progression from acute to chronic HBV infection will be further explored. Publication History Article published online: 26 January 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany