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Research Article

Optimized production and immunogenicity of an insect virus-based chikungunya virus candidate vaccine in cell culture and animal models

, , , , , , , , , , , & ORCID Icon show all
Pages 305-316 | Received 19 Nov 2020, Accepted 02 Feb 2021, Published online: 25 Feb 2021
 

ABSTRACT

A chimeric Eilat/ Chikungunya virus (EILV/CHIKV) was previously reported to replicate only in mosquito cells but capable of inducing robust adaptive immunity in animals. Here, we initially selected C7/10 cells to optimize the production of the chimeric virus. A two-step procedure produced highly purified virus stocks, which was shown to not cause hypersensitive reactions in a mouse sensitization study. We further optimized the dose and characterized the kinetics of EILV/CHIKV-induced immunity. A single dose of 108 PFU was sufficient for induction of high levels of CHIKV-specific IgM and IgG antibodies, memory B cell and CD8+ T cell responses. Compared to the live-attenuated CHIKV vaccine 181/25, EILV/CHIKV induced similar levels of CHIKV-specific memory B cells, but higher CD8+ T cell responses at day 28. It also induced stronger CD8+, but lower CD4+ T cell responses than another live-attenuated CHIKV strain (CHIKV/IRES) at day 55 post-vaccination. Lastly, the purified EILV/CHIKV triggered antiviral cytokine responses and activation of antigen presenting cell (APC)s in vivo, but did not induce APCs alone upon in vitro exposure. Overall, our results demonstrate that the EILV/CHIKV vaccine candidate is safe, inexpensive to produce and a potent inducer of both innate and adaptive immunity in mice.

Acknowledgements

We thank Dr. Alfredo Torres for the use of ImmunoSpot 4.0 analyzer, Grace Rafael, Wenqian Li for technique support, and Dr. Linsey Yeager for assisting in manuscript preparation.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

A.A., H.L., S.R.O., B.W., A.J.A., C.M.R. and K.S.P. performed the experiments. I.F., S.C.W., and T.W. designed the experiment. S.T. provided critical reagents, A.A., H.L., E.I.F., I.F., B.P. and T.W. analyzed the data. T.W. wrote the first draft of the manuscript. All authors edited the manuscript.

Additional information

Funding

This work was supported by National Institute of Allergy and Infectious Diseases [grant number R01AI127744,R01AI153433].