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

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dc.contributor.authorAdam, Awadalkareemen
dc.contributor.authorLuo, Huanleen
dc.contributor.authorOsman, Samantha R.en
dc.contributor.authorWang, Binbinen
dc.contributor.authorRoundy, Christopher M.en
dc.contributor.authorAuguste, Albert J.en
dc.contributor.authorPlante, Kenneth S.en
dc.contributor.authorPeng, Bi-Hungen
dc.contributor.authorThangamani, Saravananen
dc.contributor.authorFrolova, Elena I.en
dc.contributor.authorFrolov, Ilyaen
dc.contributor.authorWeaver, Scott C.en
dc.contributor.authorWang, Tianen
dc.contributor.departmentEntomologyen
dc.contributor.departmentFralin Life Sciences Instituteen
dc.contributor.departmentCenter for Emerging, Zoonotic, and Arthropod-borne Pathogensen
dc.date.accessioned2021-06-09T12:16:46Zen
dc.date.available2021-06-09T12:16:46Zen
dc.date.issued2021-01-01en
dc.description.abstractA 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 10(8) 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.en
dc.description.notesThis work was supported by National Institute of Allergy and Infectious Diseases [grant number R01AI127744, R01AI153433].en
dc.description.sponsorshipNational Institute of Allergy and Infectious DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [R01AI127744, R01AI153433]en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1080/22221751.2021.1886598en
dc.identifier.eissn2222-1751en
dc.identifier.issue1en
dc.identifier.pmid33539255en
dc.identifier.urihttp://hdl.handle.net/10919/103715en
dc.identifier.volume10en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectVaccineen
dc.subjectinsecten
dc.subjectimmunityen
dc.subjectChikungunya virusen
dc.subjectsafetyen
dc.titleOptimized production and immunogenicity of an insect virus-based chikungunya virus candidate vaccine in cell culture and animal modelsen
dc.title.serialEmerging Microbes & Infectionsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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