Novel attenuated chikungunya vaccine candidates elicit protective immunity in C57BL/6 mice

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Hallengard, David
Kakoulidou, Maria
Lulla, Aleksei
Kummerer, Beate M.
Johansson, Daniel X.
Mutso, Margit
Lulla, Valeria
Fazakerley, John K.
Roques, Pierre
Le Grand, Roger
Merits, Andres
Liljestrom, Peter
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2014
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Abstract

Chikungunya virus (CHIKV) is a reemerging mosquito-borne alphavirus that has caused severe epidemics in Africa and Asia and occasionally in Europe. As of today, there is no licensed vaccine available to prevent CHIKV infection. Here we describe the development and evaluation of novel CHIKV vaccine candidates that were attenuated by deleting a large part of the gene encoding nsP3 or the entire gene encoding 6K and were administered as viral particles or infectious genomes launched by DNA. The resulting attenuated mutants were genetically stable and elicited high magnitudes of binding and neutralizing antibodies as well as strong T cell responses after a single immunization in C57BL/6 mice. Subsequent challenge with a high dose of CHIKV demonstrated that the induced antibody responses protected the animals from viremia and joint swelling. The protective antibody response was long-lived, and a second homologous immunization further enhanced immune responses. In summary, this report demonstrates a straightforward means of constructing stable and efficient attenuated CHIKV vaccine candidates that can be administered either as viral particles or as infectious genomes launched by DNA.

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Journal of Virology

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88

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5

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© 2013 American Society for Microbiology. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.

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Microbiology not elsewhere classified

Biological Sciences

Agricultural and Veterinary Sciences

Medical and Health Sciences

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