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| Content Provider | PubMed Central |
|---|---|
| Author | Juan, García-arriaza Cepeda, Victoria David, Hallengärd Sorzano, Carlos Óscar S. Kümmerer, Beate Mareike Peter, Liljeström Esteban, Mariano |
| Editor | Perlman, S. |
| Copyright Year | 2014 |
| Abstract | There is a need to develop a single and highly effective vaccine against the emerging chikungunya virus (CHIKV), which causes a severe disease in humans. Here, we have generated and characterized the immunogenicity profile and the efficacy of a novel CHIKV vaccine candidate based on the highly attenuated poxvirus vector modified vaccinia virus Ankara (MVA) expressing the CHIKV C, E3, E2, 6K, and E1 structural genes (termed MVA-CHIKV). MVA-CHIKV was stable in cell culture, expressed the CHIKV structural proteins, and triggered the cytoplasmic accumulation of Golgi apparatus-derived membranes in infected human cells. Furthermore, MVA-CHIKV elicited robust innate immune responses in human macrophages and monocyte-derived dendritic cells, with production of beta interferon (IFN-β), proinflammatory cytokines, and chemokines. After immunization of C57BL/6 mice with a homologous protocol (MVA-CHIKV/MVA-CHIKV), strong, broad, polyfunctional, and durable CHIKV-specific CD8+ T cell responses were elicited. The CHIKV-specific CD8+ T cells were preferentially directed against E1 and E2 proteins and, to a lesser extent, against C protein. CHIKV-specific CD8+ memory T cells of a mainly effector memory phenotype were also induced. The humoral arm of the immune system was significantly induced, as MVA-CHIKV elicited high titers of neutralizing antibodies against CHIKV. Remarkably, a single dose of MVA-CHIKV protected all mice after a high-dose challenge with CHIKV. In summary, MVA-CHIKV is an effective vaccine against chikungunya virus infection that induced strong, broad, highly polyfunctional, and long-lasting CHIKV-specific CD8+ T cell responses, together with neutralizing antibodies against CHIKV. These results support the consideration of MVA-CHIKV as a potential vaccine candidate against CHIKV. |
| Related Links | http://dx.doi.org/10.1128/jvi.03418-13 |
| Ending Page | 3547 |
| Page Count | 21 |
| Starting Page | 3527 |
| File Format | |
| ISSN | 0022538X |
| e-ISSN | 10985514 |
| Journal | Journal of Virology |
| Issue Number | 6 |
| Volume Number | 88 |
| Language | English |
| Publisher | American Society for Microbiology |
| Publisher Date | 2014-03-15 |
| Access Restriction | Open |
| Rights Holder | American Society for Microbiology |
| Subject Keyword | Immunology Virology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Virology Immunology Microbiology Insect Science |
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