HeberNasvac (ABX203) / Center for Genetic Engineering and Biotechnology, Abivax - LARVOL DELTA

Oral Presentation: Sanitary Intervention with HeberNasvac in Cuba to Treat all HBsAg Positive Chronic Hepatitis B Patients Before 2027 (APASL 2025) - "HeberNasvac will be used as part of a large scale sanitary intervention, this product will be used as part of a technological package comprising the vaccine, a cost effective diagnostic set optimized for a massive introduction of the product, and with the use of computing technology. This approach may be a suitable option to tackle chronic hepatitis B derived fatalities in Cuba and in future in other countries as a method for CHB elimination strategy in Cuba as part of the Cuban Health System efforts to accomplish WHO goals. Patients from all countries are also welcome in specialized Cuban hospitals to receive the product as part of Health Services to be provided during the 2025-2030 campaign."

Clinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation

HeberNasvac: Development and Application in the Context of Chronic Hepatitis B. (PubMed, Euroasian J Hepatogastroenterol) - "Aguilar JC, Akbar SMF, Al-Mahtab M, et al. HeberNasvac: Development and Application in the Context of Chronic Hepatitis B. Euroasian J Hepato-Gastroenterol 2024;14(2):221-237."

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

Limited Value of HBV-RNA for Relapse Prediction After Nucleos(t)ide Analogue Withdrawal in HBeAg-negative Hepatitis B Patients. (PubMed, J Viral Hepat) - P=N/A, P2b | "The value of HBV-RNA levels at timepoint of NA cessation for the prediction of relapse is limited in HBeAg-negative patients. Trial Registration: ABX 203-002: NCT02249988; Terminator 2: NCT03643172."

Journal • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Impact of the Route and Schedule of Immunization on the Serological and Virological Response of Chronic Hepatitis B Patients Treated with HeberNasvac. (PubMed, Euroasian J Hepatogastroenterol) - "Impact of the Route and Schedule of Immunization on the Serological and Virological Response of Chronic Hepatitis B Patients Treated with HeberNasvac. Euroasian J Hepato-Gastroenterol 2023;13(2):73-78."

Journal • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Preparing for the Next Pandemic: Increased Expression of Interferon-Stimulated Genes After Local Administration of Nasalferon or HeberNasvac. (PubMed, DNA Cell Biol) - "In most cases, the gene expression induced by HeberNasvac was similar in profile and intensity to the expression induced by Nasalferon and significantly superior to that observed in untreated controls. The immune stimulatory effect of HeberNasvac on ISGs paved the way for its future use as an innate immunity stimulator in elderly persons and immunocompromised subjects or as part of Mambisa, a nasal vaccine to prevent severe acute respiratory syndrome coronavirus 2 infection."

IO biomarker • Journal • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • HLA-DRB1 • ISG15 • ISG20 • STAT1 • STAT3

[VIRTUAL] Machine learning identifies immune profile to predict virological relapse after stopping nucleos(t)ide analogue therapy in HBeAg negative chronic hepatitis B (EASL-ILC-I 2020) - P2b | " In a post-hoc analysis of a prospective, multicenter therapeutic vaccination trial (ABX-203, NCT02249988) HBsAg, HBcrAg, and 47 SIMs were repeatedly determined before NA was stopped... Host immune markers such as SIMs seem to be an underestimated marker for guiding treatment cessation in HBeAg negative CHB patients. Machine learning emerged as a valuable tool to predict SIM patterns that allow a precise identification of patients particularly suitable for NA cessation."

Hepatitis B • Hepatology • Infectious Disease • CCL5 • IL17A • IL2

Action Mechanisms and Scientific Rationale of Using Nasal Vaccine (HeberNasvac) for the Treatment of Chronic Hepatitis B. (PubMed, Vaccines (Basel)) - "Aimed at understanding the clinical results of Nasvac and other therapeutic vaccines under development, we discuss the rationale of administering a therapeutic vaccine through the nasal route and also the current alternatives to combine therapeutic vaccines and antivirals (NUCs). We also disclose potential applications of this product in novel fields of immunotherapy."

Journal • Review • Developmental Disorders • Hepatitis B • Hepatology • Immunology • Infectious Disease • Inflammation • Respiratory Diseases

Low anti-HBc levels are associated with lower risk of virological relapse after nucleos(t)ide analogue cessation in HBe antigen negative patients. (PubMed, Liver Int) - P2b | "In contrast to predominantly HBeAg positive cohorts, in our cohort of HBeAg negative patients lower anti-HBc levels are associated with a significantly lower relapse-risk after nucleos(t)ide analog cessation. The vast majority of included patients were either genotype B or C and the applicability to other genotypes has to be further evaluated. However, anti-HBc level as an indicator of the host response might be prospectively further explored for prediction models."

Journal • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Limited value of HBV-RNA levels for the prediction of relapse after discontinuation of nucleos(t)ide analogue therapy in HBe antigen negative chronic hepatitis B patients (EASL-ILC 2022) - P2b | " Serum level of HBV-RNA, HBsAg and HBcrAg were determined in 154 HBeAg negative patients, participating in a prospective, multicenter therapeutic vaccination trial (ABX-203, NCT02249988) or in an observational register trial (Terminator 2), before stop of NA therapy...Two thirds of patients were treated with entecavir (n = 94/154; 61%), while the rest received tenofovir... In a cohort of exclusively HBeAg negative patients no improvement in relapse predictionwas achieved by considering HBVRNA BL levels."

Clinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Innate Immune Stimulation Should not be Overlooked in Post-exposure Prophylaxis and Early Therapy for Coronavirus Infections. (PubMed, MEDICC Rev) - "Our group completed several HeberNasvac studies in healthy volunteers and patients with respiratory infections, and is currently starting large clinical trials in patients with early SARS-CoV-2 infections. This nasal formulation of hepatitis B vaccine has demonstrated its capacity to stimulate innate immunity markers (TLR3, TLR7 and TLR8 in tonsils) at the virus' entry site, in systemic compartments (HLA class II in monocytes and lymphocytes) and in the activation of dendritic cells, lymphocytes and other cell lines in vitro and ex vivo. In addition, research generated by the current pandemic may obtain results useful for treating other acute respiratory infections, which have long been main drivers of mortality among older adults and in early childhood."

Journal • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Otorhinolaryngology • Respiratory Diseases • Respiratory Syncytial Virus Infections • TLR3 • TLR7 • TLR8

HeberNasvac, a Therapeutic Vaccine for Chronic Hepatitis B, Stimulates Local and Systemic Markers of Innate Immunity: Potential Use in SARS-CoV-2 Postexposure Prophylaxis. (PubMed, Euroasian J Hepatogastroenterol) - "HeberNasvac, a Therapeutic Vaccine for Chronic Hepatitis B, Stimulates Local and Systemic Markers of Innate Immunity: Potential Use in SARS-CoV-2 Postexposure Prophylaxis. Euroasian J Hepato-Gastroenterol 2021;11(2):59-70."

Clinical • IO biomarker • Journal • Dengue Fever • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Hepatology • Immune Modulation • Infectious Disease • Inflammation • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Solid Tumor

Cuban Prophylactic and Therapeutic Vaccines for Controlling Hepatitis B. (PubMed, MEDICC Rev) - "Using its platform, researchers designed an innovative version of the vaccine that was the precursor of a therapeutic nasal/subcutaneous vaccine for chronic hepatitis B, HeberNasvac. This precursor vaccine, which combines Heberbiovac HB with a recombinant antigen from the virus nucleocapsid (rHBcAg), was patented and licensed in 2015 by the Cuban regulatory authority. This article provides an overview of the progress-to-date on the development of this therapeutic vaccine, including clinical trials (some completed and others ongoing) to determine safety, efficacy and therapeutic benefits."

Journal • Fibrosis • Hepatitis B • Hepatology • Immunology • Infectious Disease • Liver Failure • Oncology • Pertussis • Respiratory Diseases • Tetanus

Pilot Study Using Machine Learning to Identify Immune Profiles for the Prediction of Early Virological Relapse After Stopping Nucleos(t)ide Analogues in HBeAg-Negative CHB. (PubMed, Hepatol Commun) - P2b | "In a post hoc analysis of a prospective, multicenter therapeutic vaccination trial (ABX-203, NCT02249988), hepatitis B surface antigen, hepatitis B core antigen, and 47 SIMs were repeatedly determined before NA was stopped...Data were validated in a different cohort of 49 patients treated with entecavir...Host immune markers such as SIMs appear to be underestimated in guiding treatment cessation in HBeAg-negative patients. Machine learning can help find predictive SIM patterns that allow a precise identification of patients particularly suitable for NA cessation."

Clinical • Journal • Hepatitis B • Hepatology • Infectious Disease

Five years follow-up of chronic hepatitis B patients immunized by nasal route with the therapeutic vaccine HeberNasvac (ILC 2018) - "In conclusion, HeberNasvac administration was not associated to any safety concern 5 years after the end of treatment. Virological, biochemical, serological variables evidenced the efficacy of this product in this difficult to treat group of patients as well as the absence of disease progression. The use of the intranasal route deserves further evaluation as most of the patients with CHB lives in countries where unsafe injections are frequent and, in addition, the nasal route may further potentiate the immune response in the liver."

Clinical • Biosimilar • Fibrosis • Immunology

Contrasting Timing of Virological Relapse after Discontinuation of Tenofovir or Entecavir in Hepatitis B e Antigen-negative Patients. (PubMed, J Infect Dis) - "We analyzed which factors are associated with timing of virological relapse in 220 Asian HBeAg-negative patients from the prospective ABX203 vaccine study. Unexpectedly, only the type of antiviral therapy was significantly associated with early virological relapse, defined as HBV DNA > 2,000 IU/ml until week 12 and occurred earlier in patients treated with tenofovir versus entecavir (median time 6 versus 24 weeks, p < 0.0001). This should be considered for future trials and monitoring of patients after treatment discontinuation."

Clinical • Journal

Five-year Follow-up of Chronic Hepatitis B Patients Immunized by Nasal Route with the Therapeutic Vaccine HeberNasvac. (PubMed, Euroasian J Hepatogastroenterol) - "Five-year Follow-up of Chronic Hepatitis B Patients Immunized by Nasal Route with the Therapeutic Vaccine HeberNasvac. Euroasian J Hepatogastroenterol, 2018;8(2):133-139."

Clinical • Journal

Development of a Nasal Therapeutic Vaccine Against Chronic Hepatitis B (APASL 2019) - "HeberNasvac induced an antiviral effect associated to a Th1 response. This antiviral response was more sustained in vaccinated than PegIFNa treated patients."