Shoushtari Mohammad, Salehi-Vaziri Mostafa, Kadkhodazadeh Maryam, Teimoori Ali, Arashkia Arash, Roohvand Farzin, Teimoori-Toolabi Ladan, Pouriayevali Mohammad Hassan, Azadmanesh Kayhan
Department of Virology Pasteur Institute of Iran Tehran Iran.
Department of Arboviruses and Viral Hemorrhagic Fevers (National Reference Laboratory) Pasteur Institute of Iran Tehran Iran.
Int Immunopharmacol. 2025 Feb 20;148:114032. doi: 10.1016/j.intimp.2025.114032. Epub 2025 Jan 19.
Dengue virus (DENV) remains a significant public health threat in tropical and subtropical regions, with effective antiviral treatments and vaccines still not fully established despite extensive research. A critical aspect of vaccine development for DENV involves selecting proteins from both structural and non-structural regions of the virus to activate humoral and cellular immune responses effectively. In this study, we developed a novel vaccine for dengue virus serotype 2 (DENV2) using a heterologous Prime-Boost strategy that combines an adenoviral vector (Ad) with subunit vaccines. The vaccine design included non-structural protein 1 (NS1), envelope protein domain III (EDIII), and the bc-loop of envelope domain II (EDII) as conserved epitopes. These antigens were fused into a single construct P1 and inserted into the pAdTrack-CMV vector to produce a recombinant adenovirus (rAd5-P1) via homologous recombination in E. coli. The examination of the immune response indicated that strong humoral and cellular immunity was generated in various groups of mice. Additionally, the group receiving a heterologous regimen of recombinant adenovirus and protein showed a superior balance of humoral and cellular immunity in terms of IgG2a/IgG1 and INF-γ /IL-4 ratios. These findings validate the vaccine design's ability to utilize both structural and non-structural proteins to generate strong immune responses on two platforms. The promising results from the heterologous regimen highlight its potential as an effective DENV2 vaccine candidate. This research offers significant insights into developing safe and effective DEN vaccines, contributing to efforts to control DENV infections.
登革病毒（DENV）在热带和亚热带地区仍然是一个重大的公共卫生威胁，尽管进行了广泛研究，但有效的抗病毒治疗方法和疫苗仍未完全确立。登革病毒疫苗开发的一个关键方面是从病毒的结构和非结构区域选择蛋白质，以有效激活体液免疫和细胞免疫反应。在本研究中，我们使用将腺病毒载体（Ad）与亚单位疫苗相结合的异源初免-加强策略，开发了一种针对登革病毒2型（DENV2）的新型疫苗。疫苗设计包括非结构蛋白1（NS1）、包膜蛋白结构域III（EDIII）和包膜结构域II（EDII）的bc环作为保守表位。这些抗原被融合到一个单一构建体P1中，并插入pAdTrack-CMV载体，通过大肠杆菌中的同源重组产生重组腺病毒（rAd5-P1）。免疫反应检测表明，各实验组小鼠均产生了强烈的体液免疫和细胞免疫。此外，接受重组腺病毒和蛋白质异源方案的组在IgG2a/IgG1和INF-γ/IL-4比率方面表现出更好的体液免疫和细胞免疫平衡。这些发现验证了疫苗设计利用结构蛋白和非结构蛋白在两个平台上产生强烈免疫反应的能力。异源方案取得的良好结果突出了其作为一种有效的DENV2疫苗候选物的潜力。这项研究为开发安全有效的登革病毒疫苗提供了重要见解，有助于控制登革病毒感染的努力。
