NUCLEOSIDE-MODIFIED MRNA VACCINES PROTECT IFNAR -/- MICE AGAINST CRIMEAN-CONGO HEMORRHAGIC FEVER VIRUS INFECTION
Intro: Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV), is the causative agent of Crimean-Congo hemorrhagic fever (CCHF). Occurrence of the virus coincides with the distribution of its primary vector and reservoir, Hyalomma ticks. Global climate changes may be a cause for the introduction of...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | International Journal of Infectious Diseases |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1201971223001595 |
| _version_ | 1797824616600698880 |
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| author | A. Mirazimi |
| author_facet | A. Mirazimi |
| author_sort | A. Mirazimi |
| collection | DOAJ |
| description | Intro: Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV), is the causative agent of Crimean-Congo hemorrhagic fever (CCHF). Occurrence of the virus coincides with the distribution of its primary vector and reservoir, Hyalomma ticks. Global climate changes may be a cause for the introduction of the Hyalomma tick to new areas and consequently, spreading of the disease. With global distribution, high fatality rate, and no approved vaccine or effective treatment, CCHF constitutes a threat against global health. Methods: CCHFV nucleoside-modified mRNA-LNP IFNAR-/- and immunocompetent mice. Findings: 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. Discussion: 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. Conclusion: 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. |
| first_indexed | 2024-03-13T10:40:38Z |
| format | Article |
| id | doaj.art-079bc38d57ef4c088fced00fd3564941 |
| institution | Directory Open Access Journal |
| issn | 1201-9712 |
| language | English |
| last_indexed | 2024-03-13T10:40:38Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal of Infectious Diseases |
| spelling | doaj.art-079bc38d57ef4c088fced00fd35649412023-05-18T04:37:58ZengElsevierInternational Journal of Infectious Diseases1201-97122023-05-01130S10S11NUCLEOSIDE-MODIFIED MRNA VACCINES PROTECT IFNAR -/- MICE AGAINST CRIMEAN-CONGO HEMORRHAGIC FEVER VIRUS INFECTIONA. Mirazimi0Karolinska Institute, LABMED, SwedenIntro: Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV), is the causative agent of Crimean-Congo hemorrhagic fever (CCHF). Occurrence of the virus coincides with the distribution of its primary vector and reservoir, Hyalomma ticks. Global climate changes may be a cause for the introduction of the Hyalomma tick to new areas and consequently, spreading of the disease. With global distribution, high fatality rate, and no approved vaccine or effective treatment, CCHF constitutes a threat against global health. Methods: CCHFV nucleoside-modified mRNA-LNP IFNAR-/- and immunocompetent mice. Findings: 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. Discussion: 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. Conclusion: 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.http://www.sciencedirect.com/science/article/pii/S1201971223001595 |
| spellingShingle | A. Mirazimi NUCLEOSIDE-MODIFIED MRNA VACCINES PROTECT IFNAR -/- MICE AGAINST CRIMEAN-CONGO HEMORRHAGIC FEVER VIRUS INFECTION International Journal of Infectious Diseases |
| title | NUCLEOSIDE-MODIFIED MRNA VACCINES PROTECT IFNAR -/- MICE AGAINST CRIMEAN-CONGO HEMORRHAGIC FEVER VIRUS INFECTION |
| title_full | NUCLEOSIDE-MODIFIED MRNA VACCINES PROTECT IFNAR -/- MICE AGAINST CRIMEAN-CONGO HEMORRHAGIC FEVER VIRUS INFECTION |
| title_fullStr | NUCLEOSIDE-MODIFIED MRNA VACCINES PROTECT IFNAR -/- MICE AGAINST CRIMEAN-CONGO HEMORRHAGIC FEVER VIRUS INFECTION |
| title_full_unstemmed | NUCLEOSIDE-MODIFIED MRNA VACCINES PROTECT IFNAR -/- MICE AGAINST CRIMEAN-CONGO HEMORRHAGIC FEVER VIRUS INFECTION |
| title_short | NUCLEOSIDE-MODIFIED MRNA VACCINES PROTECT IFNAR -/- MICE AGAINST CRIMEAN-CONGO HEMORRHAGIC FEVER VIRUS INFECTION |
| title_sort | nucleoside modified mrna vaccines protect ifnar mice against crimean congo hemorrhagic fever virus infection |
| url | http://www.sciencedirect.com/science/article/pii/S1201971223001595 |
| work_keys_str_mv | AT amirazimi nucleosidemodifiedmrnavaccinesprotectifnarmiceagainstcrimeancongohemorrhagicfevervirusinfection |