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Efficacy, Safety, and Immunogenicity of Hepatitis B Vaccines

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A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Hepatitis Virus Vaccines".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 6893

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Special Issue Editor

Dr. Benjamin J. Burwitz

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Guest Editor

Vaccine & Gene Therapy Institute, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA
Interests: viral immunology; non-human primate transgenics; model development

Special Issue Information

Dear Colleagues,

There are currently 296 million people living with chronic hepatitis B (HepB) worldwide, and nearly 1 million of these individuals will die each year from disease-related complications. There are multiple hepatitis B vaccines approved for use by international health regulatory agencies, yet the prevalence of HepB continues to rise. This is due, in part, to HepB vaccine non-responsiveness in 5–10% of patients. This issue focuses on efforts to safely improve the efficacy of HepB vaccines by expanding our understanding of non-responsiveness, testing new adjuvants and vectors, and enhancing vaccine stability during transport, with the goal of making the HepB vaccine available and protective to larger numbers of individuals globally.

Dr. Benjamin J. Burwitz
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

hepatitis B
vaccination
non-responder

Published Papers (5 papers)

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Research

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19 pages, 6168 KiB

Open AccessArticle

mRNA Therapeutic Vaccine for Hepatitis B Demonstrates Immunogenicity and Efficacy in the AAV-HBV Mouse Model

by Dorien De Pooter, Wim Pierson, Soheil Pourshahian, Koen Dockx, Ben De Clerck, Isabel Najera, Heather Davis, Ellen Van Gulck and Daniel Boden

Vaccines 2024, 12(3), 237; https://doi.org/10.3390/vaccines12030237 - 25 Feb 2024

Viewed by 1502

Abstract

Chronic infection with hepatitis B virus (HBV) develops in millions of patients per year, despite the availability of effective prophylactic vaccines. Patients who resolve acute HBV infection develop HBV-specific polyfunctional T cells accompanied by neutralizing antibodies, while in patients with chronic hepatitis B (CHB), immune cells are dysfunctional and impaired. We describe a lipid nanoparticle (LNP)-formulated mRNA vaccine, optimized for the expression of HBV core, polymerase, and surface (preS2-S) antigens with the aim of inducing an effective immune response in patients with CHB. Prime and prime/boost vaccination with LNP-formulated mRNA encoding for core, pol, and/or preS2-S dosing strategies were compared in naive C57BL/6 and BALB/c mice. Immune responses were assessed by IFN-γ ELISpot, intracellular cytokine staining (ICS), and ELISA for antibody production, whereas anti-viral efficacy was evaluated in the AAV-HBV mouse model. The mRNA vaccine induced strong antigen-specific polyfunctional T cell responses in these mouse models, accompanied by the emergence of anti-HBs and anti-HBe antibodies. After three immunizations, the antigen-specific immune stimulation resulted in up to 1.7 log₁₀ IU/mL reduction in systemic HBV surface antigen (HBsAg), accompanied by a transient drop in systemic HBeAg, and this was observed in 50% of the AAV-HBV-transduced mice in the absence of additional modalities such as adjuvants, HBsAg reducing agents, or checkpoint inhibitors. However, no treatment-related effect on viremia was observed in the liver. These results warrant further optimization and evaluation of this mRNA vaccine as a candidate in a multimodal therapeutic regimen for the treatment of chronic HBV infection. Full article

(This article belongs to the Special Issue Efficacy, Safety, and Immunogenicity of Hepatitis B Vaccines)

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19 pages, 4597 KiB

Open AccessArticle

Sustained Liver HBsAg Loss and Clonal T- and B-Cell Expansion upon Therapeutic DNA Vaccination Require Low HBsAg Levels

by Nádia Conceição-Neto, Wim Pierson, Maurizio Vacca, Matthias Beyens, Ben De Clerck, Liese Aerts, Birgit Voeten, Dorien De Pooter, Lore Verschueren, Koen Dockx, Mathias Vandenberk, Ewoud De Troyer, Kato Verwilt, Carl Van Hove, Mieke Verslegers, Leslie Bosseler, Marjolein Crabbe, Vinod Krishna, Isabel Nájera and Ellen Van Gulck

Vaccines 2023, 11(12), 1825; https://doi.org/10.3390/vaccines11121825 - 06 Dec 2023

Cited by 1 | Viewed by 1229

Abstract

Background: Suppression of HBV DNA, inhibition of HBV surface (HBsAg) production and therapeutic vaccination to reverse HBV-specific T-cell exhaustion in chronic HBV patients are likely required to achieve a functional cure. In the AAV-HBV mouse model, therapeutic vaccination can be effective in clearing HBV when HBsAg levels are low. Using a single-cell approach, we investigated the liver immune environment with different levels of HBsAg and sustained HBsAg loss through treatment with a GalNAc-HBV-siRNA followed by therapeutic vaccination. Methods: AAV-HBV-transduced C57BL/6 mice were treated with GalNAc-HBV-siRNA to lower HBsAg levels and then vaccinated using a DNA vaccine. We used single-cell RNA and V(D)J sequencing to understand liver immune microenvironment changes. Results: GalNAc-HBV-siRNA, followed by therapeutic vaccination, achieved sustained HBsAg loss in all mice. This was accompanied by CD4 follicular helper T-cell induction, polyclonal activation of CD8 T cells and clonal expansion of plasma cells that were responsible for antibody production. Conclusions: This study provides novel insights into liver immune changes at the single-cell level, highlighting the correlation between induced reduction of HBsAg levels and clonal expansion of CD4, CD8 T cells and plasma cells in the liver upon HBV siRNA and subsequent therapeutic vaccination. Full article

(This article belongs to the Special Issue Efficacy, Safety, and Immunogenicity of Hepatitis B Vaccines)

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22 pages, 7485 KiB

Open AccessArticle

Mafosfamide Boosts GMI-HBVac against HBV via Treg Depletion in HBV-Infected Mice

by Qin Lin, Yiwei Zhong and Bin Wang

Vaccines 2023, 11(6), 1026; https://doi.org/10.3390/vaccines11061026 - 25 May 2023

Viewed by 1613

Abstract

Chronic hepatitis B infection remains a significant worldwide health burden, placing persons at risk for hepatocellular cancer and hepatic fibrosis. Chronic hepatitis B virus (CHB) infection is characterized by elevated levels of immunosuppressive regulatory T cells (Tregs), which can inhibit the function of effector T cells and lead to an insufficient immune clearance response against HBV. Theoretically, suppression of Treg cell functionality and percentage could increase anti-HBV reactivity in CHB-infected patients, although this has not yet been explored. We attempted to enhance our previously established anti-CHB protocol utilizing the GM-CSF+IFN-α+rHBVvac regimen (GMI-HBVac) by incorporating mafosfamide (MAF), which has been utilized in anticancer therapy in the past. Intravenous administration of MAF to rAAV8-1.3HBV-infected mice resulted in a dose-dependent reduction of Tregs in the blood, rebounding to pretreatment levels 10 days later. To assess the potential benefit of adding MAF to the anti-CHB protocol, 2 μg/mL MAF was combined with the GMI-HBVac as an anti-Treg treatment in an HBV-infected animal model. When rAAV8-1.3HBV-infected mice were immunized with MAF+GMI-HBVac, peripheral blood Tregs decreased significantly, leading to dendritic cell activation, HBV-specific T cell proliferation, and the upregulation of IFN-gamma-producing CD8⁺T cells. In addition, MAF+GMI-HBVac vaccination stimulated T cell infiltration in HBV-infected livers. These effects may contribute to an enhanced immune response and the clearance of HBV-associated antigens, including serum HBsAg, serum HBcAg, and HBcAg⁺ hepatocytes. Overall, this is the first indication that MAF can act as an adjuvant with GMI-HBVac to deplete Tregs in mice with an established CHB infection. This unique therapeutic vaccine regimen produced a functional cure, as revealed by the remarkable clearance of HBsAg. Full article

(This article belongs to the Special Issue Efficacy, Safety, and Immunogenicity of Hepatitis B Vaccines)

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12 pages, 958 KiB

Open AccessArticle

Efficacy of Hepatitis B Virus Vaccines HBVaxpro40© and Fendrix© in Patients with Chronic Liver Disease in Clinical Practice

by Diana Horta, Montserrat Forné, Anna Agustí, Agnes Raga, Albert Martín-Cardona, Juana María Hernández-Soto, Pablo Ruiz-Ramírez and Maria Esteve-Comas

Vaccines 2022, 10(8), 1323; https://doi.org/10.3390/vaccines10081323 - 16 Aug 2022

Cited by 2 | Viewed by 1611

Abstract

Chronic liver disease results in a low response rate to the hepatitis B virus vaccine. Information on the efficacy of the double adjuvanted vaccine FENDRIX^® (3-O-desacyl-4’-monophosphoryl lipid A and aluminum phosphate) and single adjuvant HBVAXPRO^®40 (aluminum hydroxyphosphate sulfate) in chronic liver disease is scarce. The primary aim of this prospective study in clinical practice was to evaluate the effectiveness of HBVAXPRO^®40 and FENDRIX^® in this setting. Patients received HBVAXPRO^® (0, 1 and 6 months) or FENDRIX^® (0, 1, 2 and 6 months) depending on availability. Clinical data and anti-HBs levels were collected at 2, 6 and 12 months. A total of 125 patients were included (mean age 61.8 years; 57.6% males; 43.2% liver cirrhosis; 75.9% Child A and 24.1% Child B): 76 were vaccinated with HBVAXPRO^® and 49 with FENDRIX^®. There were no significant differences between the two vaccines. The overall response rates at 2, 6 and 12 months were 76.8, 72.8 and 59.2%, respectively. In the univariate analysis, active alcohol intake, alcohol etiology, liver cirrhosis and ultrasound signs of portal hypertension were associated with a lower response to vaccination, whereas in the multivariate analysis, liver cirrhosis was the only factor that significantly increased the likelihood of nonresponse (OR 10.5). HBVAXPRO^® and FENDRIX^® are good options for HBV vaccination in patients with chronic liver disease. Full article

(This article belongs to the Special Issue Efficacy, Safety, and Immunogenicity of Hepatitis B Vaccines)

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Review

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22 pages, 1254 KiB

Open AccessReview

Hepatitis B Vaccine: Four Decades on

by Maria Mironova and Marc G. Ghany

Vaccines 2024, 12(4), 439; https://doi.org/10.3390/vaccines12040439 - 18 Apr 2024

Viewed by 427

Abstract

Hepatitis B virus is a substantial contributor to cirrhosis and hepatocellular carcinoma (HCC) globally. Vaccination is the most effective method for prevention of hepatitis B and its associated morbidity and mortality, and the only method to prevent infection with hepatitis D virus. The hepatitis B vaccine has been used worldwide for more than four decades; it is available in a single- or triple-antigen form and in combination with vaccines against other infections. Introduction of the vaccine and administration at birth led to sustained decline in mother-to-child transmission, chronic hepatitis B, and HCC, however, global birth dose coverage remains suboptimal. In this review we will discuss different hepatitis B vaccine formulations and schedules, vaccination guidelines, durability of the response, and vaccine escape mutants, as well as the clinical and economic benefits of vaccination. Full article

(This article belongs to the Special Issue Efficacy, Safety, and Immunogenicity of Hepatitis B Vaccines)

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