ORIGINAL RESEARCH article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1562107
IL-2 and IL-15 Augment HBV Therapeutic Vaccination and PD1 Blockade for Functional Cure In the AAV-HBV Mouse Model
Provisionally accepted
- Johnson and Johnson Innovative Medicine, San Diego, California, United States
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Prevalence of chronic Hepatitis B virus (HBV) infection remains a major global health issue. Research into a cure has focused on finite combinatorial interventions that aim to reduce HBV surface antigen (HBsAg), suppress virus-specific immune tolerance, and induce an adaptive response that functionally controls the virus. In C57BL/6 mice transduced with adeno-associated virus encoding the HBV genome, that replicate HBV and persistently express HBsAg at 10 4 IU/mL or higher, a combination of small interfering (si)RNA knockdown of HBsAg expression followed by immunization with a self-amplifying RNA therapeutic HBV vaccine, failed to establish HBV control. Using this in vivo murine model, we screened for immunomodulatory agents added after HBV siRNA knockdown, and in combination with therapeutic vaccination, that may enhance the HBV adaptive immune response to control HBV. In mice with very high levels of HBsAg (10 4 -10 5 IU/mL), levels that are observed clinically during standard HBV therapy, that were brought low (10 2 IU/mL) by HBV siRNA pretreatment prior to therapeutic vaccination, PDL1 blockade in combination with stabilized cytokines IL-2 or IL-15 led to immune control of HBsAg in vaccinated animals.
Keywords: Hepatitis B virus, Antiviral Agents, small interfering RNA, Vaccine immunology, Immunomodulation
Received: 17 Jan 2025; Accepted: 05 Jun 2025.
Copyright: © 2025 Lewis, Malo, Rowland, Hooks, Liu, Popli, Kukolj and Pace. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Gavin Lewis, Johnson and Johnson Innovative Medicine, San Diego, California, United States
Craig Pace, Johnson and Johnson Innovative Medicine, San Diego, California, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.