Design and Analysis of Novel HEV Vaccine Variants and Evaluation of Two Selected Candidates in a Porcine Infection Model

Background and Aims: Hepatitis E virus (HEV) poses a significant global health concern, with millions of annual infections and a notable impact on public health. Although HEV is the leading cause of acute viral hepatitis worldwide, there is a substantial lack of approved and licensed vaccines. In this study, we evaluated the efficacy of several protein- and DNA-based vaccine candidates against HEV using a combined in vitro/in vivo workflow. Methods: Corresponding vaccine candidates were produced, biochemically analysed and characterised. The general immunogenicity of suitable vaccine candidates was initially evaluated in a rabbit model. Resulting antibodies were assessed for their reactivity and neutralising efficiency. Finally, the most effective candidates were tested in a pig infection model using a prime-boost vaccination regimen. Results: Using this approach, we analysed a total of seven vaccine candidates and demonstrated that the two most promising candidates significantly reduced virus shedding in swine faecal samples after infection. However, no sterile immunity was achieved.Conclusions: This study conducted a comprehensive analysis to establish a rational approach for post-vaccination immune responses in pigs. The insights gained from this research are expected to significantly contribute to the development and evaluation of future vaccine candidates for pig herds, ultimately reducing viral dissemination among pigs and preventing HEV transmission from pigs to humans. These findings hold important translational value, offering a foundation for both improving animal health and safeguarding public health.</p

Hepatitis E virus is highly resistant to alcohol-based disinfectants

Background The Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide and mainly transmitted via the fecal-oral route or consumption of contaminated food products. Due to the lack of efficient cell culture systems for the propagation of HEV, limited data regarding HEV sensitivity to chemical disinfectants are available. Consequently, preventive and evidence-based hygienic guidelines on HEV disinfection are lacking. Methods We used a robust HEV genotype 3 cell culture model which allows quantification of viral infection of quasi-enveloped and naked HEV particles. For HEV genotype 1 infections the primary isolate Sar55 in a faecal suspension was applied. Standardized quantitative suspension tests using end point dilution and large-volume-plating were performed for the determination of virucidal activity of alcohols (1-propanol, 2-propanol, ethanol), WHO disinfectant formulations and five different commercial hand disinfectants against HEV. Iodixanol gradients were conducted to elucidate the influence of ethanol on quasi-enveloped viral particles. Results Naked and quasi-enveloped HEV was resistant to alcohols as well as alcohol-based formulations recommended by WHO. Of the tested commercial hand disinfectants only one product displayed a virucidal activity against HEV. This activity could be linked to phosphoric acid as essential ingredient. Finally, we observed that ethanol and possibly non-active alcohol-based disinfectants disrupt the quasi-envelope structure of HEV particles, while leaving the highly transmissible and infectious naked virions intact. Conclusions Different alcohols and alcohol-based hand disinfectants were insufficient to eliminate HEV infectivity with the exception of one commercial ethanol-based product including phosphoric acid. These findings have strong implications for the efficient prevention measures to reduce viral transmission in clinical practice. Lay summary Hepatitis E virus (HEV) showed a strong stability against alcohols and alcohol-based hand disinfectants. With phosphoric acid one essential substance could be identified to active ethanol in its virucidal activity against HEV, which allows to improve hygiene measures for the prevention of HEV transmissions

Functional and immunogenic characterization of diverse HCV glycoprotein E2 variants

© 2018 European Association for the Study of the Liver Background & Aims: Induction of cross-reactive antibodies targeting conserved epitopes of the envelope proteins E1E2 is a key requirement for an hepatitis C virus vaccine. Conserved epitopes like the viral CD81-binding site are targeted by rare broadly neutralizing antibodies. However, these viral segments are occluded by variable regions and glycans. We aimed to identify antigens exposing conserved epitopes and to characterize their immunogenicity. Methods: We created hepatitis C virus variants with mutated glycosylation sites and/or hypervariable region 1 (HVR1). Exposure of the CD81 binding site and conserved epitopes was quantified by soluble CD81 and antibody interaction and neutralization assays. E2 or E1-E2 heterodimers with mutations causing epitope exposure were used to immunize mice. Vaccine-induced antibodies were examined and compared with patient-derived antibodies. Results: Mutant viruses bound soluble CD81 and antibodies targeting the CD81 binding site with enhanced efficacy. Mice immunized with E2 or E1E2 heterodimers incorporating these modifications mounted strong, cross-binding, and non-interfering antibodies. E2-induced antibodies neutralized the autologous virus but they were not cross-neutralizing. Conclusions: Viruses lacking the HVR1 and selected glycosylation sites expose the CD81 binding site and cross-neutralization antibody epitopes. Recombinant E2 proteins carrying these modifications induce strong cross-binding but not cross-neutralizing antibodies. Lay summary: Conserved viral epitopes can be made considerably more accessible for binding of potently neutralizing antibodies by deletion of hypervariable region 1 and selected glycosylation sites. Recombinant E2 proteins carrying these mutations are unable to elicit cross-neutralizing antibodies suggesting that exposure of conserved epitopes is not sufficient to focus antibody responses on production of cross-neutralizing antibodies

Orientierung schaffen

Zusammenfassung. Aktuell wird vielfach über Ansätze einer demenzorientierte Umgebungsgestaltung in Altenpflegeeinrichtungen berichtet und diskutiert. Aber wie sieht es mit der Implementierung der Ergebnisse in der Praxis aus? In einem Projekt an der Krankenpflegeschule des Städtischen Klinikums Dessau stellen sich Schülerinnen und Schüler der Gesundheits- und Krankenpflege dieser Herausforderung und suchen am Beispiel einer stationären Altenpflegeeinrichtung nach praktikablen Möglichkeiten der Umsetzung. </jats:p

Impfstoffe gegen Hepatitis E: Wo stehen wir?

ZusammenfassungIn Europa ist aktuell kein Impfstoff gegen das Hepatitis-E-Virus (HEV) zugelassen. Demgegenüber steht in China bereits seit 10 Jahren mit HEV-239 (Hecolin®, Xiamen Innovax Biotech Co., Xiamen, China) ein Vakzin gegen den HEV-Genotyp 4 zur Verfügung. Herausforderungen für die Entwicklung von Impfstoffen ergeben sich v. a. aus den Unterschieden zwischen den Genotypen bezüglich Verbreitung, Übertragungswege und Risikogruppen. Weitere Hindernisse sind die Umhüllung von HEV im Blut durch Wirtsmembranen, die Replikation in verschiedenen Organen außerhalb der Leber sowie schwächere Immunantworten in vulnerablen Gruppen. In diesem Artikel wird der aktuelle Stand der verfügbaren und in fortgeschrittener präklinischer Evaluation befindlichen Vakzine gegen HEV mit Fokus auf Strategien der Impfstoffentwicklung dargestellt. Herausforderungen und Limitationen werden beschrieben.Aktuelle Impfkandidaten fokussieren auf proteinbasierte Immunisierungen mit dem Ziel der Induktion von schützenden, neutralisierenden Antikörperantworten. Das Ziel der HEV-239-Zulassungsstudie mit mehr als 100.000 Studienteilnehmern war die Verhinderung von akuten symptomatischen Infektionen. Es ist jedoch unklar, inwieweit asymptomatische Infektionen durch das Vakzin verhindert wurden und ob es in Risikopatienten für einen komplizierten Verlauf, wie Patienten mit Leberzirrhose, Immunsupprimierten und Schwangeren, effektiv genug wirkt. Effiziente In-vitro-Modelle ermöglichen zunehmend die Entwicklung von monoklonalen neutralisierenden Antikörpern zur passiven Immunisierung oder Therapie.Zukünftige Vakzine sollten neben einem sehr guten Sicherheitsprofil eine eindeutige Protektion gegenüber allen Genotypen demonstrieren. Die Entwicklung einer effizienten passiven Immunisierungsstrategie, insbesondere für immunsupprimierte Personen, ist wünschenswert.</jats:p