Assessment of Immunogenicity and Neutralisation Efficacy of Viral-Vectored Vaccines Against Chikungunya Virus

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.

A Single and Un-Adjuvanted Dose of a Chimpanzee Adenovirus-Vectored Vaccine against Chikungunya Virus Fully Protects Mice from Lethal Disease

“…Given that the ChAdOx1 CHIK vaccines described here are safe and effective, further characterization, including dosing and long-term immunogenicity studies in C57Bl/6 mice is warranted. The ChAdOx1 vectored vaccines described here were designed to express a multi-lineage mosaic protein with the aim to widen protection against all CHIKV lineages [14]. We hypothesized that as neutralizing antibodies against the CHIKV surface antigens correlate with protection, the capsid being the most internal structural protein might be less of a requirement to induce effective immunity.…”

“…Transgenes were cloned into a pMono plasmid, under the control of a CMV promoter. More details have been described before [14]. ChAdOx1 Zika (Zika prME ∆TM) was used as a negative control [13].…”

“…We have developed two ChAdOx1 vaccines that induce swift and robust anti-CHIKV immune responses upon a single dose, without the need for adjuvants or booster doses [14]. ChAdOx1 Chik (formerly known as ChAdOx1 sCHIKV) encodes a cassette expressing all CHIKV structural proteins (capsid, E3, E2, 6k, and E1), while ChAdOx1 Chik ∆Cap (formerly known as ChAdOx1 sCHIKV ∆C) expresses all structural proteins but the capsid.…”

Recent Progress in Vaccine Development Against Chikungunya Virus

“…Due to the induction of anti-adenovirus immune response, human adenoviral-vectored vaccines are not suitable for humans. Chimpanzee adenovirus overcomes this problem to maintain vaccine efficacy (Lopez-Camacho et al, 2019). In this study, the full length or capsid-deleted structural proteins of CHIKV were expressed at the adenoviral platform to generated vaccines ChAdOx1 sCHIKV and ChAdOx1 sCHIKV C. A single dose of the two kinds of ChAdOx1 vaccines was injected in BALB/c mice.…”

Adenoviral-Vectored Mayaro and Chikungunya Virus Vaccine Candidates Afford Partial Cross-Protection From Lethal Challenge in A129 Mouse Model

“…ChAdOx1 has deletions on the E1 and E3 genes that render it replication-deficient thereby enhancing its safety ( 32 ). We have previously reported that ChAdOx1 encoding CHIKV structural proteins (ChAdOx1 Chik) elicits long-lasting IgG antibodies against CHIKV E2 in BALB/c mice ( 33 ). ELISA measurements at two weeks, six weeks and 10 months post vaccination, showed that the levels of IgG anti-CHIKV E2 are maintained over time, suggesting long term immunity of at least 10 months.…”