Autor(es): García-Arriaza Juan, Cepeda Victoria, Hallengärd David, Sorzano Carlos Óscar S, Kümmerer Beate Mareike, Liljeström Peter, Esteban Mariano

Resumo: There is a need to develop a single - highly effective vaccine against the emerging chikungunya virus (CHIKV), which causes a severe disease in humans. Here, we have generated - characterized the immunogenicity profile - the efficacy of a novel CHIKV vaccine c-idate based on the highly attenuated poxvirus vector modified vaccinia virus Ankara (MVA) expressing the CHIKV C, E3, E2, 6K, - E1 structural genes (termed MVA-CHIKV). MVA-CHIKV was stable in cell culture, expressed the CHIKV structural proteins, - triggered the cytoplasmic accumulation of Golgi apparatus-derived membranes in infected human cells. Furthermore, MVA-CHIKV elicited robust innate immune responses in human macrophages - monocyte-derived dendritic cells, with production of beta interferon (IFN-?), proinflammatory cytokines, - chemokines. After immunization of C57BL/6 mice with a homologous protocol (MVA-CHIKV/MVA-CHIKV), strong, broad, polyfunctional, - durable CHIKV-specific CD8(+) T cell responses were elicited. The CHIKV-specific CD8(+) T cells were preferentially directed against E1 - E2 proteins -, 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, - 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 c-idate against CHIKV. We have developed a novel vaccine c-idate against chikungunya virus (CHIKV) based on the highly attenuated poxvirus vector modified vaccinia virus Ankara (MVA) expressing the CHIKV C, E3, E2, 6K, - E1 structural genes (termed MVA-CHIKV). Our findings revealed that MVA-CHIKV is a highly effective vaccine against chikungunya virus, with a single dose of the vaccine protecting all mice after a high-dose challenge with CHIKV. Furthermore, MVA-CHIKV is highly immunogenic, inducing strong innate responses: high, broad, polyfunctional, - long-lasting CHIKV-specific CD8(+) T cell responses, together with neutralizing antibodies against CHIKV. This work provides a potential vaccine c-idate against CHIKV.

Imprenta: Journal of Virology, v. 88, n. 6, p. 3527-3547, 2014

Identificador do objeto digital: 10.1128/JVI.03418-13

Descritores: Chikungunya virus - Cell ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Antibodies ; Chikungunya virus - Cytokines ; Chikungunya virus - T lymphocytes ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Immunology ; Chikungunya virus - Public health

Data de publicação: 2014

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