Autor(es): Weger-Lucarelli James, Chu Haiyan, Aliota Matthew T, Partidos Charalambos D, Osorio Jorge E

Resumo: Chikungunya virus (CHIKV) is a re-emerging arbovirus associated with febrile illness often accompanied by rash - arthralgia that may persist for several years. Outbreaks are associated with high morbidity - create a public health challenge for countries affected. Recent outbreaks have occurred in both Europe - the Americas, suggesting CHIKV may continue to spread. Despite the sustained threat of the virus, there is no approved vaccine or antiviral therapy against CHIKV. Therefore, it is critical to develop a vaccine that is both well tolerated - highly protective. In this study, we describe the construction - characterization of a modified Vaccinia virus Ankara (MVA) virus expressing CHIKV E3 - E2 proteins (MVA-CHIK) that protected several mouse models from challenge with CHIKV. In particular, BALB/c mice were completely protected against viremia upon challenge with CHIKV after two doses of MVA-CHIK. Additionally, A129 mice (deficient in IFN?/?) were protected from viremia, footpad swelling, - mortality. While high anti-virus antibodies were elicited, low or undetectable levels of neutralizing antibodies were produced in both mouse models. However, passive transfer of MVA-CHIK immune serum to naïve mice did not protect against mortality, suggesting that antibodies may not be the main effectors of protection afforded by MVA-CHIK. Furthermore, depletion of CD4(+), but not CD8(+) T-cells from vaccinated mice resulted in 100% mortality, implicating the indispensable role of CD4(+) T-cells in the protection afforded by MVA-CHIK. The results presented herein demonstrate the potential of MVA to effectively express CHIKV E3-E2 proteins - generate protective immune responses. Our findings challenge the assumption that only neutralizing antibodies are effective in providing protection against CHIKV, - provides a framework for the development of novel, more effective vaccine strategies to combat CHIKV.

Imprenta: PLoS Neglected Tropical Diseases, v. 8, n. 7, p. e2970, 2014

Identificador do objeto digital: 10.1371/journal.pntd.0002970

Descritores: Chikungunya virus - Arbovirus ; Chikungunya virus - Cell ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Antibodies ; 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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