Investigation of cellular and humoral immune responses induced by SARS-CoV-2 VLP vaccine in Pre-clinical and clinical studies

buir.advisorGürsel, İhsan
dc.contributor.authorBildik, Kadriye Tuğçe
dc.date.accessioned2022-08-31T12:47:42Z
dc.date.available2022-08-31T12:47:42Z
dc.date.copyright2022-08
dc.date.issued2022-08
dc.date.submitted2022-08-29
dc.descriptionCataloged from PDF version of article.en_US
dc.descriptionThesis (Master's): Bilkent University, Department of Molecular Biology and Genetics, İhsan Doğramacı Bilkent University, 2022.en_US
dc.descriptionIncludes bibliographical references (leaves 60-70).en_US
dc.description.abstractCOVID-19 pandemic, caused by SARS-CoV-2, emerged in China in late 2019, and as of March 2020 has become a serious concern for the whole world due to severe progression of the disease especially in the elderly and high transmission rate of the virus. The ravages of pandemic on health sector, economy and social life accelerated the vaccine race as vaccination is the most critical measure to hamper the pace of the pandemic and the most important step for acquiring herd immunity. Various vaccine studies are registered by WHO most of which target Spike protein or a certain region of Spike protein, such as receptor binding domain (RBD) for inducing immune reactions. Alternatively, the use of virus-like particle (VLP) technology for vaccine development broadens the magnitude of immune responses as the four main structural proteins of the virus, Spike, Nucleocapsid, Membrane and Envelope, are incorporated. Therefore, we developed a VLP vaccine against SARS-CoV-2 and adjuvanted it using Alum and K3 CpG ODN. Herein, we investigated the humoral and cellular immune responses induced by SARS-CoV-2 VLP vaccine in pre-clinical and clinical studies. The results from pre-clinical experiments conducted on vaccinated BALB/c mice indicated that VLP vaccine triggered effective antibody response against Spike, Nucleocapsid, Wild Type RBD, Alpha RBD and Delta RBD proteins as shown by ELISA. Additionally, it was proven that the diminishing antibody responses can be boosted and a prolonged immune response was achieved by a third dose of VLP vaccine. For the clinical studies, the humoral and cellular immune responses of Phase II clinical trial volunteers were analyzed by employing ELISA and CBA methods respectively. The results obtained from ELISA demonstrated that the Phase II volunteers developed effective antibody titers against Spike, Nucleocapsid, Wild Type RBD, Alpha RBD and Delta RBD proteins. Analysis of the cellular immune responses by CBA showed that VLP vaccine induced a Th1-skewed immune reaction with coexistence of Th2-, Th17- and Treg related responses owing to its formulation with K3 CpG ODN and Alum. Taken together, our results indicated that SARS-CoV-2 VLP accine triggered effective cellular and humoral immune reactions against Spike and Nucleocapsid along with RBD variants which proved the cross-protective response achieved. Elicitation of multi-functional immune response and adoptability of the VLP technology to newly emerging variants makes VLP vaccine a promising candidate for the future booster injections.en_US
dc.description.provenanceSubmitted by Betül Özen (ozen@bilkent.edu.tr) on 2022-08-31T12:47:42Z No. of bitstreams: 1 B161230.pdf: 4904261 bytes, checksum: b3a7851e391b5c182632489903fbe2f5 (MD5)en
dc.description.provenanceMade available in DSpace on 2022-08-31T12:47:42Z (GMT). No. of bitstreams: 1 B161230.pdf: 4904261 bytes, checksum: b3a7851e391b5c182632489903fbe2f5 (MD5) Previous issue date: 2022-08en
dc.description.statementofresponsibilityby Kadriye Tuğçe Bildiken_US
dc.embargo.release2023-02-20
dc.format.extentxiv, 123 leaves : illustrations ; 30 cm.en_US
dc.identifier.itemidB161230
dc.identifier.urihttp://hdl.handle.net/11693/110482
dc.language.isoEnglishen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectCOVID-19en_US
dc.subjectSARS-CoV-2en_US
dc.subjectVirus-like particleen_US
dc.subjectVaccineen_US
dc.subjectK3 CpG ODNen_US
dc.subjectHumoral immune response Cellular immune responseen_US
dc.titleInvestigation of cellular and humoral immune responses induced by SARS-CoV-2 VLP vaccine in Pre-clinical and clinical studiesen_US
dc.title.alternativeSARS-COV-2 VLP aşısına karşı geliştirilen hümoral ve hücresel immün yanıtların klinik öncesi ve klinik çalışmalarda incelenmesien_US
dc.typeThesisen_US
thesis.degree.disciplineMolecular Biology and Genetics
thesis.degree.grantorBilkent University
thesis.degree.levelMaster's
thesis.degree.nameMS (Master of Science)

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