Development and characterization of novel dendritic cell (DC)-targeting vaccine against human immunodeficiency virus (HIV)-1 envelope conserved elements (CEs)

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Mahmoudi, Mona
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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.
HIV, Virus-Like particle vaccine, Conserved Regions, Macrophages