Expression and Characterization of Yeast Derived Chikungunya Virus Like Particles (CHIK-VLPs) and Its Evaluation as a Potential Vaccine Candidate

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dc.contributor.authorSaraswat, Shwetaen
dc.contributor.authorAthmaram, T. N.en
dc.contributor.authorParida, Manmohanen
dc.contributor.authorAgarwal, Ankitaen
dc.contributor.authorSaha, Amritaen
dc.contributor.authorDash, Paban Kumaren
dc.date.accessioned2019-08-09T14:43:24Zen
dc.date.available2019-08-09T14:43:24Zen
dc.date.issued2016-07en
dc.description.abstractChikungunya virus (CHIKV) has emerged as a global health concern due to its recent spread in both old and new world. So far, no CHIKV specific drug or vaccine is licensed for human use. In this study, we report production of Chikungunya virus like particles (CHIK-VLPs) using novel yeast expression system (Pichia pastoris) and its evaluation as vaccine candidate. The gene encoding structural polyprotein of CHIKV from a recent epidemic strain was cloned into yeast expression system. The multicopy integrants were processed for expression of CHIK-VLPs. The VLPs were purified and confirmed through electron microscopic analysis for their morphological identity with CHIKV. The in vitro and in vivo evaluation of CHIK-VLPs as vaccine candidate was determined in Balb/c mice. Induction of both humoral and cellular immune response was observed with different doses of CHIK-VLPs. The humoral immune response was studied through different techniques like enzyme linked immunosorbent assay, IgG Isotyping and plaque reduction neutralization test. CHIK-VLPs were found to elicit high titer of antibodies that are able to recognize native CHIKV. Higher level of IgG2a and IgG1 subtypes was identified suggestive of balanced Th1/Th2 response. Both in vitro and in vivo neutralization activity of CHIK-VLPs antibodies was observed even with low concentration, which shows its high specificity and neutralizing activity against two different CHIKV strains. Neonatal mice receiving anti-CHIK-VLPs antibodies were protected from CHIKV challenge. Induction of cellular immune response was confirmed through higher level of TNF-alpha, IL-10 and substantial level of IL-2, IL-4 and IFN-gamma indicating a balanced response. This is the first report, where CHIK-VLPs has been expressed by Pichia pastoris and evaluated for neutralizing activity against CHIKV. These promising results indicate the utility of CHIK-VLPs as a promising vaccine candidate against emerging CHIKV.en
dc.description.notesThis work was funded by Defence Research Development Organization, Ministry of Defence, Govt of India. The authors are thankful to the Director, Defence Research Development Establishment (DRDE), Gwalior for his keen interest and support in this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.description.sponsorshipDefence Research Development Organization, Ministry of Defence, Govt of Indiaen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pntd.0004782en
dc.identifier.issn1935-2735en
dc.identifier.issue7en
dc.identifier.othere0004782en
dc.identifier.pmid27399001en
dc.identifier.urihttp://hdl.handle.net/10919/93023en
dc.identifier.volume10en
dc.language.isoenen
dc.publisherPLOSen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectpichia-pastorisen
dc.subjectprotein expressionen
dc.subjectecsa genotypeen
dc.subjectmouse modelen
dc.subjectmiceen
dc.subjectdiseaseen
dc.subjectimmunogenicityen
dc.subjectimmunityen
dc.titleExpression and Characterization of Yeast Derived Chikungunya Virus Like Particles (CHIK-VLPs) and Its Evaluation as a Potential Vaccine Candidateen
dc.title.serialPLOS Neglected Tropical Diseasesen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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