Novel bioinformatics approaches to design epitope-based vaccine against HIV latency by inquiring CTL epitopes and built-in adjuvants

利用新型生物信息学方法,通过研究 CTL 表位和内置佐剂,设计针对 HIV 潜伏感染的基于表位的疫苗

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Abstract

A key characteristic of HIV-1 persistence under antiretroviral therapy is its ability to form a latent reservoir in T cells, creating an obstacle to the virus eradication, therefore, there is no effective and permanent treatment against HIV-1. This study aims to develop an epitope-based vaccine that targets HIV-1's key CTL epitopes involved in infection and latency. After studying and carefully checking previous reports and immunoinformatics, a multi-epitope vaccine was designed with strong CTL (Gag p24 and Pol) epitopes. CPP peptide (Tat) and an adjuvant (β-defensin) were incorporated into the vaccine construct for cell entry and to improve immunogenicity. The designed vaccine was evaluated in terms of antigenicity, allergenicity, safety, various physicochemical properties, solubility, and molecular docking with TLR4 using in silico tools. Immune simulation predicted a significant induction of immune responses. Successful expression and purification of the recombinant protein in E. coli BL21 strain, followed by confirmation by Western blot, demonstrated the feasibility of the vaccine production. Finally, our findings suggest that the designed epitope-based vaccine can induce humoral and cellular immune responses and is a suitable candidate for an HIV-1 therapeutic vaccine to control infection and latency.

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