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

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

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

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

A Heterologous Protein Prime/MVA Boost Therapeutic Hepatitis B Vaccine Candidate (clinicaltrials.gov) - P1a | N=24 | Not yet recruiting | Sponsor: Universitätsklinikum Hamburg-Eppendorf

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

Efficient stabilization of therapeutic hepatitis B vaccine components by amino-acid formulation maintains its potential to break immune tolerance. (PubMed, JHEP Rep) - "The therapeutic hepatitis B vaccine TherVacB combines protein priming with a Modified Vaccinia virus Ankara (MVA)-vector boost to break immune tolerance in chronic HBV infection...In this study, the authors developed thermostable vaccine components that are well tolerated and that induce immune responses and control the virus in preclinical mouse models, even after long-term exposure to high surrounding temperatures. This will lower costs and ease application of a therapeutic vaccine and thus be beneficial for the many people affected by hepatitis B around the world."

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

Activation of CD4 T cells during prime immunization determines the success of a therapeutic hepatitis B vaccine in HBV-carrier mouse models. (PubMed, J Hepatol) - "Our results identify CD4 T-cell activation during the priming phase as a key determinant for HBV-specific antibody and CD8 T cell immunity using TherVacB as targeted therapeutic vaccine."

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

PD-L1 Silencing in Liver Using siRNAs Enhances Efficacy of Therapeutic Vaccination for Chronic Hepatitis B. (PubMed, Biomolecules) - "In this study, we used small-interfering RNA (siRNA) in combination with a heterologous prime-boost therapeutic vaccination scheme (TherVacB) to interfere with a major immune checkpoint, the interaction of programmed death protein-1 (PD-1) and its ligand (PDL-1)...The antiviral effect was more pronounced if PD-L1 was down-regulated during prime than during boost vaccination. Thus, targeting PD-L1 using siRNA is a promising approach to enhance the efficacy of therapeutic vaccination and finally cure HBV."

Journal • Hepatitis B • Hepatology • Immune Modulation • Immunology • Infectious Disease • Inflammation • Oncology • CD8 • PD-1 • PD-L1

A Non-interventional Registry for Patients With Hepatitis B Virus Infection (clinicaltrials.gov) - P=N/A; N=3000; Recruiting; Sponsor: Hannover Medical School

Clinical • New trial • Hepatitis B • Hepatology • Immune Modulation • Infectious Disease • Inflammation • IFNG • IL1B • IL6

Immunogenicity and Antiviral Response of Therapeutic Hepatitis B Vaccination in a Mouse Model of HBeAg-Negative, Persistent HBV Infection. (PubMed, Vaccines (Basel)) - "HBV-carrier mice were immunized with TherVacB, a therapeutic hepatitis B vaccine that uses a particulate HBV S and a core protein for prime vaccination, and a modified vaccinia Ankara (MVA) for boost vaccination...Intrahepatic, HBV-specific CD8 T cells induced in HBeAg(-) mice expressed more IFNγ but showed similar cytolytic activity. This indicates that the loss of HBeAg improves the performance of therapeutic vaccination by enhancing non-cytolytic effector functions."

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

"#TherVacB scientists will meet you virtually @ #ILC2021, then! Thanks for sharing the update!" (@TherVacB_EU)

[VIRTUAL] Multicistronic DNA-based therapeutic vaccine as a promising candidate to treat chronic hepatitis B virus (HBV) infection (EASL-ILC-I 2020) - "Our results show that DNA-HBVac may be a promising alternative for the classical recombinant protein priming for TherVacB regimen, without the need for labor intensive and expensive recombinant protein purification."

Hepatitis B • Hepatology • Infectious Disease • CD8