# Integrated analysis of HBV-specific CD4 T cell and B cell responses to define their role in chronic hepatitis B and HBV functional cure.

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $1,168,511

## Abstract

Project Summary
The overarching goal of this multi-PI R01 proposal is to identify the mediators of functional cure of hepatitis B
virus (HBV) infection in the cellular and humoral immune responses. Understanding the immune correlates of
HBV functional cure, but also the molecular pathways involved in the immune dysregulation leading to persistent
HBV infection and hepatitis will greatly facilitate design of effective immunotherapies and therapeutic
vaccinations. HBV chronically infects >250 million people and remains a significant public health burden, despite
the availability of an effective prophylactic vaccine for more than 30 years. While some infected individuals can
naturally control viral replication, known as functional cure, the required immune conditions, particularly in the
CD4 T cell and B cell responses, are undefined. Similarly, the exact mechanisms of how HBV-specific CD4 T
cell and B cell responses are subverted in persistent infection remains unclear. In this study, we will study the
immune responses of well-defined clinical cohorts across the different HBV infection outcomes. The two aims
are: (1) to define HBV-specific CD4 T cell functions and the molecular signatures important in immune
suppression versus cure; (2) to define HCV-specific humoral responses and the molecular signatures in B cells
associated with viral pathogenesis and cure. The two highly complementary and synergistic aims will be
analyzed in a highly integrated systems approach, allowing novel understanding of how CD4 T cells, antibodies
and B cells synergize in order to control HBV infection. By using the same tissue specimens from the clinical
cohorts for all we will achieve a holistic and integrated understanding of the immune landscapes presented in
the different manifestations caused by HBV infection. The results have the potential to guide novel
immunotherapeutic approaches aimed at inducing sustained control of HBV without the need for life-long antiviral
treatments.

## Key facts

- **NIH application ID:** 10943851
- **Project number:** 1R01AI184931-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** GEORG Michael LAUER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,168,511
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10943851

## Citation

> US National Institutes of Health, RePORTER application 10943851, Integrated analysis of HBV-specific CD4 T cell and B cell responses to define their role in chronic hepatitis B and HBV functional cure. (1R01AI184931-01). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10943851. Licensed CC0.

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