Development and characterization of novel dendritic cell (DC)-targeting vaccine against human immunodeficiency virus (HIV)-1 envelope conserved elements (CEs)
| dc.contributor.author | Mahmoudi, Mona | |
| dc.contributor.examiningcommittee | McClarty, Grant (Medical Microbiology and Infectious Diseases) Mizuno, Tooru (Physiology and Pathophysiology) | en_US |
| dc.contributor.supervisor | Yao, Xiaojian (Medical Microbiology and Infectious Diseases) | en_US |
| dc.date.accessioned | 2021-06-02T20:34:00Z | |
| dc.date.available | 2021-06-02T20:34:00Z | |
| dc.date.copyright | 2021-06-02 | |
| dc.date.issued | 2021-05-31 | en_US |
| dc.date.submitted | 2021-06-02T16:54:30Z | en_US |
| dc.degree.discipline | Medical Microbiology and Infectious Diseases | en_US |
| dc.degree.level | Master of Science (M.Sc.) | en_US |
| dc.description.abstract | Development of the human immunodeficiency virus type-1 (HIV-1) vaccine is an effective and powerful prevention method of the halting pandemic of the acquired immunodeficiency syndrome (AIDS). Dendritic cell (DC)-based HIV immunotherapeutic vaccine is very promising at optimizing the HIV-specific immune responses. Since the Ebola virus glycoprotein (EboGP) has strong DC-targeting ability, we hypothesized that the infusion of the highly conserved elements (CE) of HIV envelope glycoprotein including the MembraneProximal External Region (MPER), with the DC-targeting domains of EboGP (EboGPΔM), can direct these epitopes to the DCs/Macrophages and more efficiently elicit immunes responses in the host. It is known that the mucin-like domain of Ebola GP is highly glycosylated, less conserved and dispensable for EBOV infection. In this study, we have replaced the mucin-like domain of Ebola GP with 9 arranged highly conserved elements (9CE) or MPER of HIV envelop glycoprotein to generate plasmids encoding EboGPΔM-9CE, EboGPΔM-MPER to test our hypothesis. To investigate whether these fusion proteins are able to efficiently enter DCs/Macrophages, we co-transfected 293T cells with HIV vector (∆RI/∆E/Gluc), HIV packaging plasmid (Δ8.2), and EboGP∆M-9CE and/or EboGP∆M-MPER plasmids to generate virus-like particles (VLPs) and used to infect human monocytes and Macrophages. Our results have shown that EboGP∆M-9CE- and/or EboGP∆M-MPER- VLPs can efficiently target a human monocytic cell line (THP-1) and monocyte-derived macrophages (MDMs). Also, we investigated the immunogenicity of EboGPΔM-9CE-and/or EboGP∆M-MPER and/or HIV Env(M)VLPs in in vivo study in BALB/C mice and evaluated the potential T cell- and B cellmediated immune responses of the VLPs based vaccines. | en_US |
| dc.description.note | October 2021 | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/35686 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.subject | HIV | en_US |
| dc.subject | Virus-Like particle vaccine | en_US |
| dc.subject | Conserved Regions | en_US |
| dc.subject | Macrophages | en_US |
| dc.title | Development and characterization of novel dendritic cell (DC)-targeting vaccine against human immunodeficiency virus (HIV)-1 envelope conserved elements (CEs) | en_US |
| dc.type | master thesis | en_US |
| local.subject.manitoba | yes | en_US |