Abstract
Chikungunya virus (CHIKV) is an emerging mosquito-borne alphavirus indigenous to tropical Africa and Asia. Acute illness is characterized by fever, arthralgias, conjunctivitis, rash, and sometimes arthritis. Relatively little is known about the antigenic targets for immunity, and no licensed vaccines or therapeutics are currently available for the pathogen. While the Aedes aegypti mosquito is its primary vector, recent evidence suggests that other carriers can transmit CHIKV thus raising concerns about its spread outside of natural endemic areas to new countries including the U.S. and Europe. Considering the potential for pandemic spread, understanding the development of immunity is paramount to the development of effective counter measures against CHIKV. In this study, we isolated a new CHIKV virus from an acutely infected human patient and developed a defined viral challenge stock in mice that allowed us to study viral pathogenesis and develop a viral neutralization assay. We then constructed a synthetic DNA vaccine delivered by in vivo electroporation (EP) that expresses a component of the CHIKV envelope glycoprotein and used this model to evaluate its efficacy. Vaccination induced robust antigen-specific cellular and humoral immune responses, which individually were capable of providing protection against CHIKV challenge in mice. Furthermore, vaccine studies in rhesus macaques demonstrated induction of nAb responses, which mimicked those induced in convalescent human patient sera. These data suggest a protective role for nAb against CHIKV disease and support further study of envelope-based CHIKV DNA vaccines.
Highlights
Chikungunya virus (CHIKV) is an enveloped, single-stranded, positive-sense RNA virus that belongs to the family Togaviridae, genus Alphavirus, and is part of the Semliki Forest virus antigenic complex [1,2,3,4]
Chikungunya fever epidemics are sustained by a cycle of human-mosquito-human transmission, with the epidemic cycle being similar to those of dengue and urban yellow fever
We isolated CHIKV virus from an acutely infected human patient and used this new virus to develop a neutralization assay and a challenge stock, which is effective in a mouse model
Summary
Chikungunya virus (CHIKV) is an enveloped, single-stranded, positive-sense RNA virus that belongs to the family Togaviridae, genus Alphavirus, and is part of the Semliki Forest virus antigenic complex [1,2,3,4]. CHIKV has been responsible for unprecedented, explosive outbreaks during 2004 and 2007 in India and the Indian Ocean islands [2,4,5,6,7]. These outbreaks represent the largest documented cases associated with the virus [8]. CHIKV has been identified as the agent responsible for major epidemics in both Africa and Southeast Asia and continues to be a re-emerging agent of great interest to public health [1,11,12,13]. Despite its importance as an emerging virus and potential biological weapon, there are no specific licensed vaccines or antiviral treatments for Chikungunya
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