Abstract

The emerging arthritogenic, mosquito-borne chikungunya virus (CHIKV) causes severe disease in humans and represents a serious public health threat in countries where Aedes spp mosquitoes are present. This study describes for the first time the successful production of CHIKV virus-like particles (VLPs) in insect cells using recombinant baculoviruses. This well-established expression system is rapidly scalable to volumes required for epidemic responses and proved well suited for processing of CHIKV glycoproteins and production of enveloped VLPs. Herein we show that a single immunization with 1 µg of non-adjuvanted CHIKV VLPs induced high titer neutralizing antibody responses and provided complete protection against viraemia and joint inflammation upon challenge with the Réunion Island CHIKV strain in an adult wild-type mouse model of CHIKV disease. CHIKV VLPs produced in insect cells using recombinant baculoviruses thus represents as a new, safe, non-replicating and effective vaccine candidate against CHIKV infections.

Highlights

  • Chikungunya virus (CHIKV) is a mosquito-borne, singlestranded, positive-sense RNA virus that has caused sporadic outbreaks every 2–50 years of predominantly rheumatic disease, primarily in Africa and Asia

  • CHIKV is transmitted by the Asian Tiger mosquito, which is making ground to more temperate regions such as Europe, and thereby increasing the risk of CHIKV infections

  • This study describes the development of a virus-like particle (VLP) vaccine against CHIKV infections, which is produced in insect cells

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Summary

Introduction

Chikungunya virus (CHIKV) is a mosquito-borne, singlestranded, positive-sense RNA virus (genus alphavirus) that has caused sporadic outbreaks every 2–50 years of predominantly rheumatic disease, primarily in Africa and Asia. CHIKV recently (2004–2011) produced the largest epidemic recorded for an alphavirus with an estimated 1.4 to 6 million patients, and imported cases reported in nearly 40 countries including Europe, Japan and the USA. The first autochthonous CHIKV infections in Europe (Italy in 2007 and France in 2010) were seen during this epidemic. The US Army has long recognized that CHIKV could be used as a biological weapon [3]. Arthropathy usually progressively resolves over weeks to months, usually without long-term sequelae; CHIKV infections can sometimes cause severe disease manifestations and mortality [2,4]

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