Abstract
Chikungunya virus (CHIKV) has caused extensive outbreaks in several countries within the Americas, Asia, Oceanic/Pacific Islands, and Europe. In humans, CHIKV infections cause a debilitating disease with acute febrile illness and long-term polyarthralgia. Acute and chronic symptoms impose a major economic burden to health systems and contribute to poverty in affected countries. An efficacious vaccine would be an important step towards decreasing the disease burden caused by CHIKV infection. Despite no licensed vaccine is yet available for CHIKV, there is strong evidence of effective asymptomatic viral clearance due to neutralising antibodies against the viral structural proteins. We have designed viral-vectored vaccines to express the structural proteins of CHIKV, using the replication-deficient chimpanzee adenoviral platform, ChAdOx1. Expression of the CHIKV antigens results in the formation of chikungunya virus-like particles. Our vaccines induce high frequencies of anti-chikungunya specific T-cell responses as well as high titres of anti-CHIKV E2 antibodies with high capacity for in vitro neutralisation. Our results indicate the potential for further clinical development of the ChAdOx1 vaccine platform in CHIKV vaccinology.
Highlights
Chikungunya virus (CHIKV) is transmitted by Aedes mosquitoes and it is an important growing human health concern in many countries, causing significant outbreaks of acute febrile illness and long-term arthropathy [1]
In this work we have constructed CHIKV vaccines based on viral-vector platforms, such as
The immunogen was designed based on a mosaic consensus sequence from the Asian, East, Central and South African and West African regions
Summary
Chikungunya virus (CHIKV) is transmitted by Aedes mosquitoes and it is an important growing human health concern in many countries, causing significant outbreaks of acute febrile illness and long-term arthropathy [1]. Its origins are traced to Africa as an enzootic spillover, belonging to the Semliki Forest Complex of the Alphavirus (Togaviridae) [2] and was first isolated from a human patient in Tanzania in 1952 [3] Several institutions are engaged in the development of a safe and cost-effective CHIKV vaccine; such vaccines [18,19,20] are based on live-attenuated or inactivated CHIKV, chimeric CHIKV, DNA, subunit, virus-like particle (VLP) and viral-vectored platforms They are mainly designed to induce humoral responses against the structural viral protein E2, as well as E1, due to strong correlates of protection with neutralising antibodies against structural CHIKV proteins in asymptomatic cases [21]. We describe the design and development of CHIKV vaccines based on the clinically relevant adenoviral vector, ChAdOx1 and the Modified Vaccinia
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