Induction of hepatitis E virus anti-ORF3 antibodies from systemic administration of a muscle-specific Adeno-associated virus (AAV) vector

• Verfasst von: Maurer, Lars [VerfasserIn]
• Verfasst von: El Andari, Jihad [VerfasserIn]
• Verfasst von: Rapti, Kleopatra [VerfasserIn]
• Verfasst von: Spreyer, Laura [VerfasserIn]
• Verfasst von: Steinmann, Eike [VerfasserIn]
• Verfasst von: Grimm, Dirk [VerfasserIn]
• Verfasst von: Dao Thi, Viet Loan [VerfasserIn]
• Titel: Induction of hepatitis E virus anti-ORF3 antibodies from systemic administration of a muscle-specific Adeno-associated virus (AAV) vector
• Verf.angabe: Lars Maurer, Jihad El Andari, Kleopatra Rapti, Laura Spreyer, Eike Steinmann, Dirk Grimm and Viet Loan Dao Thi
• E-Jahr: 2022
• Jahr: 27 January 2022
• Umfang: 14 S.
• Fussnoten: Gesehen am 20.04.2022
• Titel Quelle: Enthalten in: Viruses
• Ort Quelle: Basel : MDPI, 2009
• Jahr Quelle: 2022
• Band/Heft Quelle: 14(2022), 2, Artikel-ID 266, Seite 1-14
• ISSN Quelle: 1999-4915
• DOI: doi:10.3390/v14020266
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: AAV
• Sach-SW: adeno-associated virus
• Sach-SW: hepatitis E virus
• Sach-SW: HEV
• Sach-SW: neutralisation
• Sach-SW: vector-based vaccine
• K10plus-PPN: 1799869938

Abstract

The hepatitis E virus (HEV) is a major global health problem, leading to large outbreaks in the developing world and chronic infections in the developed world. HEV is a non-enveloped virus, which circulates in the blood in a quasi-enveloped form. The quasi-envelope protects HEV particles from neutralising anti-capsid antibodies in the serum; however, most vaccine approaches are designed to induce an immune response against the HEV capsid. In this study, we explored systemic in vivo administration of a novel synthetic and myotropic Adeno-associated virus vector (AAVMYO3) to express the small HEV phosphoprotein ORF3 (found on quasi-enveloped HEV) in the musculature of mice, resulting in the robust and dose-dependent formation of anti-ORF3 antibodies. Neutralisation assays using the serum of ORF3 AAV-transduced mice showed a modest inhibitory effect on the infection of quasi-enveloped HEV in vivo, comparable to previously characterised anti-ORF3 antibodies used as a control. The novel AAVMYO3 capsid used in this study can serve as a versatile platform for the continued development of vector-based vaccines against HEV and other infectious agents, which could complement traditional vaccines akin to the current positive experience with SARS-CoV-2.