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JCI Insight. 2017 Mar 23;2(6):e83527. doi: 10.1172/jci.insight.83527.

Attenuated and vectored vaccines protect nonhuman primates against Chikungunya virus.

Author information

1
Université Paris Sud, UMR 1184, Orsay, France.; CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT center,; Inserm, U1184, Center for immunology of viral infections and autoimmune diseases, Fontenay aux Roses, France.
2
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
3
Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.
4
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
5
Valneva Austria Gmbh.
6
Institute of Technology, University of Tartu, Tartu, Estonia.

Abstract

Chikungunya virus (CHIKV) is rapidly spreading across the globe, and millions are infected. Morbidity due to this virus is a serious threat to public health, but at present, there is no vaccine against this debilitating disease. We have recently developed a number of vaccine candidates, and here we have evaluated 3 of them in a nonhuman primate model. A single immunization with an attenuated strain of CHIKV (Δ5nsP3), a homologous prime-boost immunization with a DNA-launched RNA replicon encoding CHIKV envelope proteins (DREP-E), and a DREP-E prime followed by a recombinant modified vaccinia virus Ankara encoding CHIKV capsid and envelope (MVA-CE) boost all induced protection against WT CHIKV infection. The attenuated Δ5nsP3 virus proved to be safe and did not show any clinical signs typically associated with WT CHIKV infections such as fever, skin rash, lymphopenia, or joint swelling. These vaccines are based on an East/Central/South African strain of Indian Ocean lineage, but they also generated neutralizing antibodies against an isolate of the Asian genotype that now is rapidly spreading across the Americas. These results form the basis for clinical development of an efficacious CHIKV vaccine that generates both humoral and cellular immunity with long-term immunological memory.

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