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- Title
Effective Chikungunya Virus-like Particle Vaccine Produced in Insect Cells.
- Authors
Metz, Stefan W.; Gardner, Joy; Geertsema, Corinne; Le, Thuy T.; Goh, Lucas; Vlak, Just M.; Suhrbier, Andreas; Pijlman, Gorben P.
- 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. Author Summary: Viruses that are transmitted by mosquitoes represent major threats for human health all over the world. One of these viruses is the Chikungunya virus (CHIKV). 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. The virus causes severe fevers and long lasting joint pains. Unfortunately, there is no vaccine to combat CHIKV infections. This study describes the development of a virus-like particle (VLP) vaccine against CHIKV infections, which is produced in insect cells. VLPs are structurally identical to the wild type virus, but these particles cannot replicate due to the absence of the viral genome. The CHIKV VLPs that were produced using the baculovirus-insect cell expression system, were correctly produced and mimic live CHIKV in structural organisation and protein function. Interestingly, a single administration of a low dose (1 µg/mouse) of non-adjuvanted VLPs induced robust neutralizing antibody titers and provided complete protection upon CHIKV challenge against viraemia and disease symptoms. This new effective, safe and scalable vaccine candidate represents a step forward in the prevention of CHIKV infections.
- Subjects
VIRUS-like particles; CHIKUNGUNYA; CHIKUNGUNYA virus; JOINT pain; SYMPTOMS; ALPHAVIRUSES
- Publication
PLoS Neglected Tropical Diseases, 2013, Vol 7, Issue 3, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0002124