Browsing by Subject "Virus-like particle"
Now showing 1 - 2 of 2
Results Per Page
Sort Options
Item Open Access Development and preclinical evaluation of virus-like particle vaccine against COVID-19 infection(Wiley-Blackwell Publishing Ltd., 2021-09-14) Yılmaz, İsmail Cem; İpekoğlu, E. M.; Bülbül, Artun; Turay, Nilsu; Yıldırım, Muzaffer; Evcili, İrem; Yılmaz, N. S.; Güvençli, N.; Aydın, Y.; Güngör, Bilgi; Saraydar, Berfu; Bartan, Aslı Gülce; İbibik, Bilgehan; Bildik, Tuğçe; Baydemir, İ.; Şanlı, H. A.; Kayaoğlu, B.; Ceylan, Yasemin; Yıldırım, Tuğçe; Abraş, İrem; Ayanoğlu, C.; Cam, S. B.; Dede, E. C.; Gizer, M.; Erganis, O.; Saraç, F.; Uzar, S.; Enul, H.; Adıay, C.; Aykut, Gamze; Polat, H.; Yıldırım, İ. S.; Tekin, S.; Körüklüoğlu, G.; Zeytin, H. E.; Korkusuz, P.; Gürsel, İhsan; Gürsel, M.Background Vaccines that incorporate multiple SARS-CoV-2 antigens can further broaden the breadth of virus-specific cellular and humoral immunity. This study describes the development and immunogenicity of SARS-CoV-2 VLP vaccine that incorporates the four structural proteins of SARS-CoV-2. Methods VLPs were generated in transiently transfected HEK293 cells, purified by multimodal chromatography, and characterized by tunable-resistive pulse sensing, AFM, SEM, and TEM. Immunoblotting studies verified the protein identities of VLPs. Cellular and humoral immune responses of immunized animals demonstrated the immune potency of the formulated VLP vaccine. Results Transiently transfected HEK293 cells reproducibly generated vesicular VLPs that were similar in size to and expressing all four structural proteins of SARS-CoV-2. Alum adsorbed, K3-CpG ODN-adjuvanted VLPs elicited high titer anti-S, anti-RBD, anti-N IgG, triggered multifunctional Th1-biased T-cell responses, reduced virus load, and prevented lung pathology upon live virus challenge in vaccinated animals. Conclusion These data suggest that VLPs expressing all four structural protein antigens of SARS-CoV-2 are immunogenic and can protect animals from developing COVID-19 infection following vaccination.Item Open Access Investigation of cellular and humoral immune responses induced by SARS-CoV-2 VLP vaccine in Pre-clinical and clinical studies(Bilkent University, 2022-08) Bildik, Kadriye TuğçeCOVID-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.