TherVacB / German Center for Infection Research, German Research Center for Environmental Health, Technical University of Munich - LARVOL DELTA

High HBV antigen levels drive loss of vaccine-induced CD8+ T-cell function in carrier mice over time. (PubMed, JHEP Rep) - "These findings identify critical time points that influence vaccine-induced CD8 T-cell responses, suggesting that early intervention targeting T-cell dysfunction may enhance therapeutic vaccination outcomes in chronic HBV infection."

IO biomarker • Journal • Preclinical • Hepatitis B • Infectious Disease • Inflammation • CD8 • PD-1

Long-term antigen reduction does not achieve durable HBV control in mice but enhances therapeutic vaccine efficacy. (PubMed, JHEP Rep) - "Our data show that, in addition to suppressing viral antigens, immune stimulation is necessary to achieve long-lasting HBV control after therapy discontinuation. These results will help design clinical trials that can ultimately achieve HBV control."

Journal • Preclinical • Hepatitis B • Infectious Disease • Inflammation

TherVacB - A Heterologous Protein Prime/MVA Boost Therapeutic Hepatitis B Vaccine Candidate (clinicaltrials.gov) - P1/2 | N=81 | Recruiting | Sponsor: Michael Hoelscher | Enrolling by invitation ➔ Recruiting

Enrollment status • Hepatitis B • Infectious Disease • Inflammation

A Heterologous Protein Prime/MVA Boost Therapeutic Hepatitis B Vaccine Candidate (clinicaltrials.gov) - P1 | N=26 | Completed | Sponsor: Universitätsklinikum Hamburg-Eppendorf | Recruiting ➔ Completed | Trial primary completion date: Feb 2026 ➔ May 2026

Trial completion • Trial primary completion date • Hepatitis B • Infectious Disease • Inflammation

Therapeutic hepatitis B vaccine employing DNA prime - MVA boost scheme requires additional priming with recombinant HBsAg to elicit an adequate antibody response. (PubMed, Front Immunol) - "We developed a therapeutic hepatitis B vaccine, TherVacB, which employs priming with adjuvanted HBV S (HBsAg) and Core antigens of a single genotype, and a boost with a pan-genotypic Modified Vaccinia Ankara vector (MVA-HBVac) expressing several viral proteins that cover more than 95% of HBV circulating strains...Our study demonstrates that although DNA can successfully prime an effective antiviral CD8+ T-cell response, it requires additional immunization with adjuvanted HBsAg to elicit satisfactory neutralizing antibody titers. In addition, it demonstrates that the sequence of immunizations in multicomponent heterologous-prime boost regimens is crucial and can significantly affect the quantity and quality of induced immune responses."

Journal • Hepatitis B • Infectious Disease • Inflammation • CD8

Protein Priming Followed by a Replication-Competent VSV-GP Vector Boost Induces Sustained Immune Control in Therapeutic Hepatitis B Vaccination. (PubMed, Vaccines (Basel)) - "Background/Objectives: Eliciting robust immune responses against the hepatitis B virus (HBV) through therapeutic vaccination holds promise for curing chronic hepatitis B. We previously developed the heterologous protein prime/viral vector boost clinical vaccine candidate, TherVacB. Long-term analyses performed 10 weeks after the last vaccination further demonstrated that a single protein-prime/VSV-GP-HBs/c boost was sufficient to achieve sustained antiviral control. These findings identify VSV-GP-HBs/c as an effective boost vector for therapeutic hepatitis B vaccination and establish protein priming followed by a single viral vector boost as an optimal strategy for sustained antiviral immunity."

Journal • Hepatitis B • Infectious Disease • Inflammation • CD4 • CD8 • IFNG

Safety and immunogenicity of a heterologous protein prime/MVA boost therapeutic hepatitis B vaccine: first results of the TherVacB phase Ia trial (ESCMID Global 2026) - No abstract available

Clinical • Late-breaking abstract • P1 data • Hepatitis B • Hepatology • Infectious Disease • Inflammation

MVA-HBVac-A novel vaccine vector that allows pan-genotypic targeting of hepatitis B virus by therapeutic vaccination. (PubMed, Mol Ther Nucleic Acids) - "This induced a sustained antiviral effect against different, clinically relevant HBV genotypes. Our data showed that the TherVacB regimen employing the novel, pan-genotypic MVA-HBVac vector could overcome HBV-specific immune tolerance and lead to the initiation of clinical trials evaluating the therapeutic vaccine."

Journal • Hepatitis B • Infectious Disease • Inflammation • CD4 • CD8

TherVacB - A Heterologous Protein Prime/MVA Boost Therapeutic Hepatitis B Vaccine Candidate (clinicaltrials.gov) - P1/2 | N=89 | Enrolling by invitation | Sponsor: Michael Hoelscher | Not yet recruiting ➔ Enrolling by invitation

Enrollment open • Hepatitis B • Infectious Disease • Inflammation

Circulating CD8 T cells are sentinels for intrahepatic T cell responses during HBV infection (EASL 2025) - "As such, immune therapies such as therapeutic vaccin- ation (TherVacB) aim to generate virus-specific T-cells to control infection... Our results identify distinct markers on HBV-specific CD8 T cells that are equally present on circulating and intrahepatic CD8 T cells and predict immune control of infection. The proprietary biomarker set allows the study of intrahepatic HBV-specific CD8 T cells by targeted analysis of circulating HBV-specific CD8 T cells and enables monitoring of immune therapies in CHB patients using peripheral blood, rather than liver biopsies."

Hepatitis B • Hepatitis C • Hepatology • Infectious Disease • Inflammation • Influenza • Respiratory Diseases • CD8 • CXCR6

A Heterologous Protein Prime/MVA Boost Therapeutic Hepatitis B Vaccine Candidate (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Universitätsklinikum Hamburg-Eppendorf | Trial primary completion date: Feb 2025 ➔ Feb 2026 | Trial completion date: Aug 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Prolonged exposure to HBV suppresses the immunogenicity and antiviral efficacy of therapeutic vaccination (EASL 2025) - "Prolonged exposure to HBV antigens resulted in more pronounced immune tolerance and significantly decreased the effector B- and T-cell responses induced by therapeutic vaccination without inducing a classical exhaustion phenotype."

Clinical • IO biomarker • Hepatitis B • Hepatology • Inflammation • CD8 • GZMB • IFNG

In vivo stimulation of 4-1BB signaling enhances the efficacy of therapeutic vaccination in high-titer hepatitis B virus carrier mice (EASL 2025) - "Combining TherVacB with 4-1BB stimulation improved HBV-specific CD8 T-cell functionality and enhanced the antiviral efficacy of TherVacB. This demonstrates that 4-1BB represents a promising therapeutic target to counteract T-cell dysfunctionality in high-titer HBV carriers."

Preclinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation • CD8

TherVacB - A Heterologous Protein Prime/MVA Boost Therapeutic Hepatitis B Vaccine Candidate (clinicaltrials.gov) - P1/2 | N=89 | Not yet recruiting | Sponsor: Michael Hoelscher | Initiation date: Dec 2024 ➔ May 2025

Trial initiation date • Hepatitis B • Hepatology • Infectious Disease • Inflammation

A Non-interventional Registry for Patients with Hepatitis B Virus Infection (clinicaltrials.gov) - P=N/A | N=3000 | Recruiting | Sponsor: Hannover Medical School | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial primary completion date • Hepatitis B • Hepatology • Infectious Disease • Inflammation

TherVacB - A Heterologous Protein Prime/MVA Boost Therapeutic Hepatitis B Vaccine Candidate (clinicaltrials.gov) - P1/2 | N=89 | Not yet recruiting | Sponsor: Michael Hoelscher | Initiation date: Jul 2024 ➔ Dec 2024

Trial initiation date • Hepatitis B • Hepatology • Infectious Disease • Inflammation

TherVacB - A Heterologous Protein Prime/MVA Boost Therapeutic Hepatitis B Vaccine Candidate (clinicaltrials.gov) - P1/2 | N=89 | Not yet recruiting | Sponsor: Michael Hoelscher

New P1/2 trial • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Development of a replication-competent Vesicular Stomatitis Virus (VSV) vector for therapeutic hepatitis B vaccination (EASL-ILC 2024) - "Background and Aims: Eliciting robust immune responses against hepatitis B virus (HBV) through therapeutic vaccination holds significant promise to cure chronic hepatitis B. We have developed a heterologous prime-boost clinical vaccine candidate, TherVacB, employing a protein-prime with recombinant HBV surface and core antigens (HBsAg, HBcAg), and a vector-boost with recombinant Modified Vaccinia virus Ankara vector (MVA) expressing HBV antigens. The protein-prime/vector-boost strategy stands as a promising and optimal therapeutic vaccine approach to cure chronic hepatitis B, in which VSV-GP-HBs/c could efficiently serve as a boost viral vector."

Hepatitis B • Hepatology • Infectious Disease • Inflammation

Development of a replication-competent Vesicular Stomatitis Virus (VSV) vector for therapeutic hepatitis B vaccination (EASL-ILC 2024) - "Background and Aims: Eliciting robust immune responses against hepatitis B virus (HBV) through therapeutic vaccination holds significant promise to cure chronic hepatitis B. We have developed a heterologous prime-boost clinical vaccine candidate, TherVacB, employing a protein-prime with recombinant HBV surface and core antigens (HBsAg, HBcAg), and a vector-boost with recombinant Modified Vaccinia virus Ankara vector (MVA) expressing HBV antigens. The protein-prime/vector-boost strategy stands as a promising and optimal therapeutic vaccine approach to cure chronic hepatitis B, in which VSV-GP-HBs/c could efficiently serve as a boost viral vector."

Hepatitis B • Hepatology • Infectious Disease • Inflammation

The combination of therapeutic vaccination with siRNA-mediated silencing of HBV and PD-L1 effectively breaks HBV-specific immunotolerance in high-titer HBV carrier mice (EASL-ILC 2024) - "Reducing HBV levels before vaccination by HBV-specific siRNAs (siHBV) enhanced the immunogenicity and antiviral efficacy of our clinical candidate protein-prime/MVA-boost therapeutic vaccine, TherVacB, in higher-titer HBV-carrier mice... Our data demonstrate that complementary siRNA-mediated silencing of HBV and the immune checkpoint PD-L1 helps to further enhance the efficacy of therapeutic vaccination in high-titer HBV carriers."

IO biomarker • Preclinical • Hepatitis B • CD8 • PD-L1

Introducing adjuvant-loaded particulate hepatitis B core antigen as an alternative therapeutic hepatitis B vaccine component. (PubMed, JHEP Rep) - "Using the heterologous protein-prime, viral-vector-boost therapeutic hepatitis B vaccine TherVacB, we compared the properties of different HBcoreAg forms...In this preclinical study, we show that loading HBcoreAg with defined nucleic-acid-based adjuvants on the one hand stabilizes the HBcoreAg with standardized capsid content and, on the other hand, efficiently promotes the immunity of HBcoreAg and a co-administered antigen, allowing for reduced adjuvant doses. Therefore, adjuvant-loaded HBcoreAg not only serves as an encouraging option for therapeutic hepatitis B vaccines, but could also act as an efficient adjuvant delivery system for other types of vaccine."

Journal • Hepatitis B • Hepatology • Infectious Disease • Inflammation

A Heterologous Protein Prime/MVA Boost Therapeutic Hepatitis B Vaccine Candidate (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Universitätsklinikum Hamburg-Eppendorf | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatitis B • Hepatology • Infectious Disease • Inflammation

A Heterologous Protein Prime/MVA Boost Therapeutic Hepatitis B Vaccine Candidate (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Universitätsklinikum Hamburg-Eppendorf | Phase classification: P1a ➔ P1 | Trial completion date: Aug 2024 ➔ Aug 2025 | Trial primary completion date: Jun 2024 ➔ Feb 2025

Phase classification • Trial completion date • Trial primary completion date • Hepatitis B • Hepatology • Infectious Disease • Inflammation

A Non-interventional Registry for Patients With Hepatitis B Virus Infection (clinicaltrials.gov) - P=N/A | N=3000 | Recruiting | Sponsor: Hannover Medical School | Trial primary completion date: May 2022 ➔ Dec 2024

Trial primary completion date • Hepatitis B • Hepatology • Infectious Disease • Inflammation • IFNG • IL1B • IL6

RECOMBINANT MOSAIC HBV CAPSID PARTICLES FOSTER ADAPTIVE IMMUNITY AGAINST THE MOST PREVALENT HBV GENOTYPES BY THERAPEUTIC VACCINATION (AASLD 2023) - "We successfully designed and expressed highly functional and immunogenic mosaic capsid particles from a single vector that can now be used in TherVacB clinical trials. Our approach provides a promising treatment strategy to cure chronic hepatitis B targeting all major circulating HBV genotypes worldwide."

Hepatitis B • Hepatology • Infectious Disease • Inflammation • CD4 • CD8