Details

Autor(en) / Beteiligte

• Krähling, Verena
• Erbar, Stephanie
• Kupke, Alexandra
• Nogueira, Sara S.
• Walzer, Kerstin C.
• Berger, Hendrik
• Dietzel, Erik
• Halwe, Sandro
• Rohde, Cornelius
• Sauerhering, Lucie
• Aragão-Santiago, Letícia
• Moreno Herrero, Jorge
• Witzel, Sonja
• Haas, Heinrich
• Becker, Stephan
• Sahin, Ugur

Titel

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

Ist Teil von

• Molecular therapy, 2023-02, Vol.31 (2), p.374-386

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• 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. [Display omitted] Our results show that self-amplifying RNAs (saRNAs), which encode both the Ebola virus glycoprotein and nucleoprotein, are a promising vaccine candidate. A single intramuscular vaccination of a combination of both saRNAs formulated in lipid nanoparticles protected 100% of mice from lethal Ebola infection and drastically reduced signs of disease.