The Johns Hopkins Medicine-led, multinational Hepatitis B and HIV Cure Consortium, colloquially known as the BICC, was recently established through the awarding of a five-year, $24 million grant from the National Institutes of Health's National Institute of Allergy and Infectious Diseases (NIAID).
The consortium ― comprised of research groups in Brazil, India, Senegal, Uganda and the United States — will use translational medicine ("translating" laboratory science into patient care applications, also known as "bench-to-bedside science") to seek a cure for hepatitis B, a lifelong, currently uncurable viral infection that can cause both acute or chronic disease, and in the latter state, put people at high risk of death from cirrhosis or liver cancer.
"Although hepatitis B can be prevented by a safe and effective vaccine given shortly after birth, it's still a major health problem worldwide, especially in areas such as the Western Pacific and Africa, where access to the birth-dose vaccine is more limited," says BICC leader Chloe Thio, M.D., professor of medicine and of molecular microbiology and immunology at the Johns Hopkins University School of Medicine. "The World Health Organization estimates that some 300 million people worldwide are already infected with hepatitis B virus [HBV], with more than a million new cases added each year ― strong evidence that the efforts of our consortium are greatly needed."
Thio says that in its first year, the major focus of the consortium is enrolling a multinational group of 450 people with HIV and chronic hepatitis B (designated as PWHHB) and 225 with just chronic hepatitis B (designated as CHB). This will be the population pool for participants in all of the consortium's research studies, as well as the sources for specimens such as blood, liver tissue, and peripheral blood mononuclear cells (primarily cells such as lymphocytes and monocytes that play important roles in immunity against diseases).
The consortium's effort toward finding a hepatitis B cure involves seven components supported by an administrative core. The components, and the team leaders from Johns Hopkins University School of Medicine and the Johns Hopkins Bloomberg School of Public Health, are:
- Virology Core (team leader Chloe Thio, M.D.): Using state-of-the-art viral diagnostic tests, this team will work with the three consortium project teams (clinical, immunology and translational) to develop and characterize blood biomarkers for HBV replication and transcription (the processes by which HBV reproduces).
- Shared Resources Core (team leader Sunil Solomon, M.B.B.S., M.P.H., Ph.D.): This team will create a human specimens repository (blood, liver tissue and peripheral blood mononuclear cells) for use by the three consortium project teams.
- Multiomics Core (team leader Winston Timp, Ph.D.): Using advanced gene sequencing and proteomics — the extensive study of proteins functioning and interacting within an organism at a specific time — this team will expand knowledge and understanding of the mechanisms by which HBV operates, providing a foundation for evaluating how the virus responds to a host, and to potential cures and treatments.
- Biostats/Data Core (team leader Bryan Lau, Ph.D.): This team will collect and analyze data from all seven consortium components.
- Clinical Project (team leader David Thomas, M.D.): This team will work with the Virology Core team and the other projects teams to perform a detailed investigation of the dynamics of HBV replication and define the host response in the blood of persons living with HBV.
- Immunology Project (team leader Justin Bailey, M.D., Ph.D.): This team will characterize the immune responses in blood and liver tissue to HBV infection during treatment.
- Translational Project (team leader Ashwin Balagopal, M.D.): Using novel molecular techniques, this team will quantify HBV genomic material and immune responses to HBV in liver tissue during treatment.
"Once the first aim of the consortium — building the cohort [enrolling the study participants] and establishing the HBV clinical and specimen repository — is completed, the second aim will be to begin studying these specimens to advance an HBV cure," says Thio. "Such studies also involve building research capacity at each of the collaborating centers and training early-stage investigators, providing a pipeline of researchers focused on finding an HBV cure."
The third aim of the consortium, Thio says, will be to study and characterize HBV persistence within the liver using novel techniques that will enhance and accelerate the understanding of how HBV reproduces, infects the cells of its host, and integrates part of its genetic instructions into the host cell's genome.
"Finally, the fourth aim of our consortium will be to use the data from all of the projects to characterize the virological and immunological dynamics of HBV infection during treatment," says Thio. "The focus will be on identifying people with good control during treatment by looking at blood levels of hepatitis B surface antigen [known as HBsAg], a protein on the surface of the HBV used to diagnose active infections and monitor response to therapy."
Thio says that using virological biomarkers, including those developed and tested in the Virology Core, the researchers will look for HBsAg loss or decline — a marker of good control — during treatment to create a multiscale mechanistic model of controlling HBV.
