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Vaccines
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Vaccines against Hepatitis Viruses
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Vaccines against Hepatitis Viruses

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

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 17638

Special Issue Editor

Dr. Dirk Wohlleber

E-Mail Website
Guest Editor
Institute of Molecular Immunology, Technical University of Munich, 80333 Munich, Germany
Interests: liver immunology; viral hepatitis

Special Issue Information

Dear Colleagues,

Hepatitis viruses cause substantial morbidity and mortality worldwide. Immune therapy in the form of vaccination is considered the best option to prevent infection and the sequelae of chronic viral hepatitis, i.e., liver cirrhosis and liver cell cancer. Despite a prophylactic vaccination against Hepatitis B that efficiently protects against infection, numbers of patients with chronic hepatitis B did not decline over the last 10 years and more than 800,000 patients die from the consequences of chronic hepatitis every year. A therapeutic vaccination is therefore needed because no curative anti-viral treatment is available so far. For hepatitis C, a curative antiviral approach has been established, but a prophylactic vaccine is required to eradicate the Hepatitis C Virus and prevent the development of viral mutants. The high mutation rate of HCV renders vaccine development difficult. For hepatitis E, a prophylactic vaccine has been developed that also prevents fulminant viral hepatitis.

This issue focuses on the current research towards immunity against viral infections of the liver. Understanding the interaction of local immune cells in the liver with hepatocytes and non-parenchymal liver cells may be crucial in developing translational approaches to establish treatment strategies to overcome chronic viral hepatitis.

Dr. Dirk Wohlleber
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

  • HBV
  • HCV
  • chronic hepatitis
  • liver
  • immunology

Published Papers (5 papers)

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Research

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17 pages, 2599 KiB  
Article
Immunogenicity and Antiviral Response of Therapeutic Hepatitis B Vaccination in a Mouse Model of HBeAg-Negative, Persistent HBV Infection
by Anna D. Kosinska, Julia Festag, Martin Mück-Häusl, Marvin M. Festag, Theresa Asen and Ulrike Protzer
Vaccines 2021, 9(8), 841; https://doi.org/10.3390/vaccines9080841 - 31 Jul 2021
Cited by 7 | Viewed by 3039
Abstract
During the natural course of chronic hepatitis B virus (HBV) infection, the hepatitis B e antigen (HBeAg) is typically lost, while the direct transmission of HBeAg-negative HBV may result in fulminant hepatitis B. While the induction of HBV-specific immune responses by therapeutic vaccination [...] Read more.
During the natural course of chronic hepatitis B virus (HBV) infection, the hepatitis B e antigen (HBeAg) is typically lost, while the direct transmission of HBeAg-negative HBV may result in fulminant hepatitis B. While the induction of HBV-specific immune responses by therapeutic vaccination is a promising, novel treatment option for chronic hepatitis B, it remains unclear whether a loss of HBeAg may influence its efficacy or tolerability. We therefore generated an adeno-associated virus (AAV)-vector that carries a 1.3-fold overlength HBV genome with a typical stop-codon mutation in the pre-core region and initiates the replication of HBeAg(−) HBV in mouse livers. Infection of C57BL/6 mice established persistent HBeAg(−) HBV-replication without any detectable anti-HBV immunity or liver damage. 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. The TherVacB immunization of HBeAg(+) and HBeAg(−) HBV carrier mice resulted in the effective induction of HBV-specific antibodies and the loss of HBsAg but only mild liver damage. 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. Full article
(This article belongs to the Special Issue Vaccines against Hepatitis Viruses)
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17 pages, 2978 KiB  
Article
Immuno-Informatics Analysis of Pakistan-Based HCV Subtype-3a for Chimeric Polypeptide Vaccine Design
by Sajjad Ahmad, Farah Shahid, Muhammad Tahir ul Qamar, Habib ur Rehman, Sumra Wajid Abbasi, Wasim Sajjad, Saba Ismail, Faris Alrumaihi, Khaled S. Allemailem, Ahmad Almatroudi and Hafiz Fahad Ullah Saeed
Vaccines 2021, 9(3), 293; https://doi.org/10.3390/vaccines9030293 - 21 Mar 2021
Cited by 27 | Viewed by 4212
Abstract
Hepatitis C virus (HCV) causes chronic and acute hepatitis infections. As there is extreme variability in the HCV genome, no approved HCV vaccine has been available so far. An effective polypeptide vaccine based on the functionally conserved epitopes will be greatly helpful in [...] Read more.
Hepatitis C virus (HCV) causes chronic and acute hepatitis infections. As there is extreme variability in the HCV genome, no approved HCV vaccine has been available so far. An effective polypeptide vaccine based on the functionally conserved epitopes will be greatly helpful in curing disease. For this purpose, an immuno-informatics study is performed based on the published HCV subtype-3a from Pakistan. First, the virus genome was translated to a polyprotein followed by a subsequent prediction of T-cell epitopes. Non-allergenic, IFN-γ producer, and antigenic epitopes were shortlisted, including 5 HTL epitopes and 4 CTL, which were linked to the final vaccine by GPGPG and AAY linkers, respectively. Beta defensin was included as an adjuvant through the EAAAK linker to improve the immunogenicity of the polypeptide. To ensure its safety and immunogenicity profile, antigenicity, allergenicity, and various physiochemical attributes of the polypeptide were evaluated. Molecular docking was conducted between TLR4 and vaccine to evaluate the binding affinity and molecular interactions. For stability assessment and binding of the vaccine-TLR4 docked complex, molecular dynamics (MD) simulation and MMGBSA binding free-energy analyses were conducted. Finally, the candidate vaccine was cloned in silico to ensure its effectiveness. The current vaccine requires future experimental confirmation to validate its effectiveness. The vaccine construct produced might be useful in providing immune protection against HCV-related infections. Full article
(This article belongs to the Special Issue Vaccines against Hepatitis Viruses)
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9 pages, 836 KiB  
Article
Fendrix® Vaccine Effectiveness in Healthcare Workers Who Are Non-Responsive to Engerix B® Vaccination
by Juan José Tejada-Pérez, Juan José Vázquez-Vicente, María Renée Herrera-Burgos, Francisco Gabriel Martín-Martín, Tesifón Parrón-Carreño and Raquel Alarcón-Rodríguez
Vaccines 2021, 9(3), 279; https://doi.org/10.3390/vaccines9030279 - 19 Mar 2021
Cited by 4 | Viewed by 2469
Abstract
Hepatitis B (HBV) is a pathogen virus with transmission mechanisms that include contact with the infected blood or bodily fluids of the infected organism. Nowadays, healthcare workers are one of the most exposed groups to HBV. Conventionally, completing a vaccine series dosage with [...] Read more.
Hepatitis B (HBV) is a pathogen virus with transmission mechanisms that include contact with the infected blood or bodily fluids of the infected organism. Nowadays, healthcare workers are one of the most exposed groups to HBV. Conventionally, completing a vaccine series dosage with Engerix B® lowers this risk by providing workers with immunity to the virus. However, through the years, we have encountered nonresponsive health personnel to the Engerix B® vaccine; hence, the Occupational Health Service of Poniente Hospital studied the Fendrix® adjuvanted vaccine as an alternative vaccine to develop immunological responses in healthcare workers who do not respond to vaccination with Engerix B®. In our study, we employed a vaccination schedule with the Fendrix® vaccine, performing serology tests on the cases after the application of each dose. The results obtained showed humoral immunity in 92.3% of the cases, with a remarkable increase in antibody titer after the first doses. These encouraging results support the future inclusion of this vaccine as one possible alternative for the immunization to HBV for healthcare workers nonresponsive to Engerix B®. Full article
(This article belongs to the Special Issue Vaccines against Hepatitis Viruses)
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11 pages, 421 KiB  
Article
Impact of Obesity and Being Overweight on the Immunogenicity to Live Attenuated Hepatitis A Vaccine in Children and Young Adults
by Termpong Dumrisilp, Jongkonnee Wongpiyabovorn, Supranee Buranapraditkun, Chomchanat Tubjaroen, Nataruks Chaijitraruch, Sittichoke Prachuapthunyachart, Palittiya Sintusek and Voranush Chongsrisawat
Vaccines 2021, 9(2), 130; https://doi.org/10.3390/vaccines9020130 - 06 Feb 2021
Cited by 4 | Viewed by 2622
Abstract
Prior results investigating a correlation between obesity and hepatitis A virus (HAV) vaccine response have been inconclusive, with limited data involving live attenuated HAV vaccines. The aim of this study is to evaluate the effect of overweight and obesity on the response to [...] Read more.
Prior results investigating a correlation between obesity and hepatitis A virus (HAV) vaccine response have been inconclusive, with limited data involving live attenuated HAV vaccines. The aim of this study is to evaluate the effect of overweight and obesity on the response to live attenuated HAV vaccine in children and young adults. This prospective cohort study was conducted in Thailand with subjects ranging in age from seven to twenty-five years. The subjects were administered 0.5 mL of MEVAC™-A and tested for anti-HAV antibodies before and at 8–9 weeks after vaccination. Baseline seronegative subjects (anti-HAV antibodies < 20 mIU/mL) were divided into non-obese (underweight/normal weight) and obese (overweight/obesity/severe obesity) groups. A total of 212 (117 non-obese and 95 obese) subjects completed the study (mean age (SD) = 13.95 (3.90) years). The seroprotection rates were 100%. Postvaccination geometric mean titers (95% CI) were 429.51 (401.97, 458.94) and 467.45 (424.47, 514.79) mIU/mL in the non-obese and obese groups, respectively. Females (p = 0.013) and subjects with truncal obesity (p = 0.002) had significantly higher titers than other participants. Live attenuated HAV vaccine is safe and has comparably high immunogenicity in both underweight/normal weight and overweight/obese persons. Full article
(This article belongs to the Special Issue Vaccines against Hepatitis Viruses)
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Review

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14 pages, 920 KiB  
Review
Improving Therapeutic Vaccination against Hepatitis B—Insights from Preclinical Models of Immune Therapy against Persistent Hepatitis B Virus Infection
by Percy A. Knolle, Li-Rung Huang, Anna Kosinska, Dirk Wohlleber and Ulrike Protzer
Vaccines 2021, 9(11), 1333; https://doi.org/10.3390/vaccines9111333 - 16 Nov 2021
Cited by 4 | Viewed by 4615
Abstract
Chronic hepatitis B affects more than 250 million individuals worldwide, putting them at risk of developing liver cirrhosis and liver cancer. While antiviral immune responses are key to eliminating hepatitis B virus (HBV) infections, insufficient antiviral immunity characterized by failure to eliminate HBV-infected [...] Read more.
Chronic hepatitis B affects more than 250 million individuals worldwide, putting them at risk of developing liver cirrhosis and liver cancer. While antiviral immune responses are key to eliminating hepatitis B virus (HBV) infections, insufficient antiviral immunity characterized by failure to eliminate HBV-infected hepatocytes is associated with chronic hepatitis B. Prophylactic vaccination against hepatitis B successfully established protective immunity against infection with the hepatitis B virus and has been instrumental in controlling hepatitis B. However, prophylactic vaccination schemes have not been successful in mounting protective immunity to eliminate HBV infections in patients with chronic hepatitis B. Here, we discuss the current knowledge on the development and efficacy of therapeutic vaccination strategies against chronic hepatitis B with particular emphasis on the pathogenetic understanding of dysfunctional anti-viral immunity. We explore the development of additional immune stimulation measures within tissues, in particular activation of immunogenic myeloid cell populations, and their use for combination with therapeutic vaccination strategies to improve the efficacy of therapeutic vaccination against chronic hepatitis B. Full article
(This article belongs to the Special Issue Vaccines against Hepatitis Viruses)
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