Self-amplifying RNA vaccine protects mice against lethal Ebola virus infection.

Autor:	Krähling V; Institute of Virology, Philipps University Marburg, Hans-Meerwein-Str. 2, 35043 Marburg, Germany; German Center for Infection Research (DZIF), Partner Site Gießen-Marburg-Langen, Marburg, Germany., Erbar S; BioNTech SE, An der Goldgrube 12, 55131 Mainz, Germany., Kupke A; Institute of Virology, Philipps University Marburg, Hans-Meerwein-Str. 2, 35043 Marburg, Germany; German Center for Infection Research (DZIF), Partner Site Gießen-Marburg-Langen, Marburg, Germany., Nogueira SS; BioNTech SE, An der Goldgrube 12, 55131 Mainz, Germany., Walzer KC; BioNTech SE, An der Goldgrube 12, 55131 Mainz, Germany., Berger H; BioNTech SE, An der Goldgrube 12, 55131 Mainz, Germany., Dietzel E; Institute of Virology, Philipps University Marburg, Hans-Meerwein-Str. 2, 35043 Marburg, Germany; German Center for Infection Research (DZIF), Partner Site Gießen-Marburg-Langen, Marburg, Germany., Halwe S; Institute of Virology, Philipps University Marburg, Hans-Meerwein-Str. 2, 35043 Marburg, Germany; German Center for Infection Research (DZIF), Partner Site Gießen-Marburg-Langen, Marburg, Germany., Rohde C; Institute of Virology, Philipps University Marburg, Hans-Meerwein-Str. 2, 35043 Marburg, Germany; German Center for Infection Research (DZIF), Partner Site Gießen-Marburg-Langen, Marburg, Germany., Sauerhering L; Institute of Virology, Philipps University Marburg, Hans-Meerwein-Str. 2, 35043 Marburg, Germany; German Center for Infection Research (DZIF), Partner Site Gießen-Marburg-Langen, Marburg, Germany., Aragão-Santiago L; BioNTech SE, An der Goldgrube 12, 55131 Mainz, Germany., Moreno Herrero J; BioNTech SE, An der Goldgrube 12, 55131 Mainz, Germany., Witzel S; TRON - Translational Oncology at the University Medical Center of the Johannes Gutenberg University gGmbH, Freiligrathstraße 12, 55131 Mainz, Germany., Haas H; BioNTech SE, An der Goldgrube 12, 55131 Mainz, Germany., Becker S; Institute of Virology, Philipps University Marburg, Hans-Meerwein-Str. 2, 35043 Marburg, Germany; German Center for Infection Research (DZIF), Partner Site Gießen-Marburg-Langen, Marburg, Germany. Electronic address: becker@staff.uni-marburg.de., Sahin U; BioNTech SE, An der Goldgrube 12, 55131 Mainz, Germany.
Jazyk:	angličtina
Zdroj:	Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2023 Feb 01; Vol. 31 (2), pp. 374-386. Date of Electronic Publication: 2022 Oct 27.
DOI:	10.1016/j.ymthe.2022.10.011
Abstrakt:	Emerging and re-emerging viruses, such as Zaire Ebola virus (EBOV), pose a global threat and require immediate countermeasures, including the rapid development of effective vaccines that are easy to manufacture. Synthetic self-amplifying RNAs (saRNAs) attend to these needs, being safe and strong immune stimulators that can be inexpensively produced in large quantities, using cell-free systems and good manufacturing practice. Here, the first goal was to develop and optimize an anti-EBOV saRNA-based vaccine in terms of its antigen composition and route of administration. Vaccinating mice with saRNAs expressing the EBOV glycoprotein (GP) alone or in combination with the nucleoprotein (NP) elicited antigen-specific immune responses. GP-specific antibodies showed neutralizing activity against EBOV. Strong CD4 + T cell response against NP and GP and CD8 + T cell response against NP were detected by ELISpot assays. Intramuscular vaccination with saRNAs conferred better immune response than intradermal. Finally, mice vaccinated in a prime-boost regimen with saRNAs encoding both GP and NP or with GP alone survived an EBOV infection. In addition, a single dose of GP and NP saRNAs was also protective against fatal EBOV infection. Overall, saRNAs expressing viral antigens represent a promising vaccine platform. Competing Interests: Declaration of interests S.E., K.W., H.B., J.M.H., and H.H. are employees and shareholders of BioNTech SE. L.A.S. is an employee of BioNTech SE. S.N. is a former employee of BioNTech SE and is currently employed by Merck KGaA. U.S. is a management board member and shareholder at BioNTech SE. S.E., J.M.H., H.H., S.B., and V.K. have a patent related to this work with the International Patent Application No. PCT/EP2022/061735 “REPLICON COMPOSITIONS AND METHODS OF USING SAME FOR THE TREATMENT OF DISEASES” BioNTech SE, TrOn GmbH, DZIF e.V., Our Ref.: 1405/PABION-167. S.H. and E.D. are former employees of the Philipps University of Marburg and are currently employed by GlaxoSmithKline. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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