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Nucleoside-Modified mRNA Vaccines Protect IFNAR -/- Mice against Crimean-Congo Hemorrhagic Fever Virus Infection

Appelberg, Sofia ; John, Lijo ; Pardi, Norbert ; Végvári, Ákos ; Bereczky, Sándor ; Ahlén, Gustaf ; Monteil, Vanessa ; Abdurahman, Samir ; Mikaeloff, Flora ; Beattie, Mitchell ; Tam, Ying ; Sällberg, Matti ; Neogi, Ujjwal ; Weissman, Drew ; Mirazimi, Ali Dutch, Rebecca Ellis

Journal of virology, 2022-02, Vol.96 (3), p.e0156821 [Periódico revisado por pares]

United States: American Society for Microbiology

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Título:
Nucleoside-Modified mRNA Vaccines Protect IFNAR -/- Mice against Crimean-Congo Hemorrhagic Fever Virus Infection
Autor: Appelberg, Sofia ; John, Lijo ; Pardi, Norbert ; Végvári, Ákos ; Bereczky, Sándor ; Ahlén, Gustaf ; Monteil, Vanessa ; Abdurahman, Samir ; Mikaeloff, Flora ; Beattie, Mitchell ; Tam, Ying ; Sällberg, Matti ; Neogi, Ujjwal ; Weissman, Drew ; Mirazimi, Ali
Dutch, Rebecca Ellis
Assuntos: Animals ; Antibodies, Neutralizing - immunology ; Antibodies, Viral - immunology ; Computational Biology - methods ; Disease Models, Animal ; Dose-Response Relationship, Immunologic ; Female ; Hemorrhagic Fever Virus, Crimean-Congo - immunology ; Hemorrhagic Fever, Crimean - prevention & control ; High-Throughput Screening Assays ; Immunization ; Immunogenicity, Vaccine ; Liposomes ; Medicin och hälsovetenskap ; Mice ; Mice, Knockout ; mRNA Vaccines - immunology ; Nanoparticles ; Proteomics - methods ; Receptor, Interferon alpha-beta - deficiency ; Vaccination ; Vaccines and Antiviral Agents ; Vaccines, Synthetic - immunology ; Virology
É parte de: Journal of virology, 2022-02, Vol.96 (3), p.e0156821
Notas: The authors declare conflicts of interest. M.S. is a founder and chairman of the board of Svenska Vaccinfabriken Produktion AB. D.W. is named on patents that describe the use of nucleoside-modified mRNA as a platform to deliver therapeutic proteins. D.W. and N.P. are named on a patent describing the use of modified mRNA in lipid nanoparticles as a vaccine platform.
Descrição: Crimean-Congo hemorrhagic fever (CCHF), caused by Crimean-Congo hemorrhagic fever virus (CCHFV), is on the World Health Organizations' list of prioritized diseases and pathogens. With global distribution, high fatality rate, and no approved vaccine or effective treatment, CCHF constitutes a threat against global health. In the current study, we demonstrate that vaccination with nucleoside-modified mRNA-lipid nanoparticles (mRNA-LNP), encoding for the CCHFV nucleoprotein (N) or glycoproteins (GcGn) protect IFNAR mice against lethal CCHFV infection. In addition, we found that both mRNA-LNP induced strong humoral and cellular immune responses in IFNAR and immunocompetent mice and that neutralizing antibodies are not necessary for protection. When evaluating immune responses induced by immunization including CCHFV Gc and Gn antigens, we found the Gc protein to be more immunogenic compared with the Gn protein. Hepatic injury is prevalent in CCHF and contributes to the severity and mortality of the disease in humans. Thus, to understand the immune response in the liver after infection and the potential effect of the vaccine, we performed a proteomic analysis on liver samples from vaccinated and control mice after CCHFV infection. Similar to observations in humans, vaccination affected the metabolic pathways. In conclusion, this study shows that a CCHFV mRNA-LNP vaccine, based on viral nucleo- or glycoproteins, mediate protection against CCHFV induced disease. Consequently, genetic immunization is an attractive approach to prevent disease caused by CCHFV and we believe we have necessary evidence to bring this vaccine platform to the next step in the development of a vaccine against CCHFV infection. Crimean-Congo hemorrhagic fever virus (CCHFV) is a zoonotic pathogen causing Crimean-Congo hemorrhagic fever (CCHF), a severe fever disease. CCHFV has a wide distribution and is endemic in several areas around the world. Cases of CCHF are also being reported in new areas, indicating an expansion of the disease, which is of high concern. Dispersion of the disease, high fatality rate, and no approved vaccine makes CCHF a threat to global health. The development of a vaccine is thus of great importance. Here we show 100% protection against lethal CCHFV infection in mice immunized with mRNA-LNP encoding for different CCHFV proteins. The vaccination showed both robust humoral and cellular immunity. mRNA-LNP vaccines combine the ability to induce an effective immune response, the safety of a transient carrier, and the flexibility of genetic vaccines. This and our results from the current study support the development of a mRNA-LNP based vaccine against CCHFV.
Editor: United States: American Society for Microbiology
Idioma: Inglês

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Nucleoside-Modified mRNA Vaccines Protect IFNAR -/- Mice against Crimean-Congo Hemorrhagic Fever Virus Infection

Appelberg, Sofia ; John, Lijo ; Pardi, Norbert ; Végvári, Ákos ; Bereczky, Sándor ; Ahlén, Gustaf ; Monteil, Vanessa ; Abdurahman, Samir ; Mikaeloff, Flora ; Beattie, Mitchell ; Tam, Ying ; Sällberg, Matti ; Neogi, Ujjwal ; Weissman, Drew ; Mirazimi, Ali Dutch, Rebecca Ellis

United States: American Society for Microbiology

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