Recombinant adenoviral vaccine encoding the spike 1 subunit of the Middle East Respiratory Syndrome Coronavirus elicits strong humoral and cellular immune responses in mice
Recombinant adenoviral vaccine encoding the spike 1 subunit of the Middle East Respiratory Syndrome Coronavirus elicits strong humoral and cellular immune responses in mice
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DOI：
10.14202/vetworld.2019.1554-1562
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发表时间：
2019-10-01
期刊：
影响因子：
1.6
通讯作者：
Khalifeh, Mohammad
中科院分区：
文献类型：
--
作者：
Ababneh, Mustafa;Alrwashdeh, Mu'men;Khalifeh, Mohammad
背景和目标：中东呼吸综合征冠状病毒 (MERS-CoV) 自 2012 年发现以来已在整个中东地区迅速传播。该病毒对全球公共卫生构成重大威胁，具有潜在的破坏性影响。在本研究中，构建了一种编码MERS-CoV基因组spike 1 (S1)亚基的重组腺病毒疫苗，并在小鼠中评估了其体液和细胞免疫反应。 材料和方法：小鼠最初通过肌肉注射进行免疫，3周后通过鼻内应用进行加强免疫。在第一次疫苗接种后第 3、4、5 和 6 周，使用针对 S1 亚单位内特定区域的常规聚合酶链反应 (PCR) 和免疫组织化学 (IHC) 检测肺和肾脏中 S1 蛋白的表达。在用 Si 蛋白 (CYSSLILDY) 内的特定 9 聚体表位进行体外刺激后，在血清和细胞培养物中评估抗原特异性体液和细胞免疫反应。 结果：首次免疫后第 6 周，通过 IHC 仅在 Ad-MERS-S1 组的肾脏中检测到 S1 蛋白表达，并在免疫后第 3 周和第 5 周通过常规 PCR 在 Ad-MERS-S1 组的肺和肾中检测到 S1 蛋白表达。该疫苗引发了特异性 S1-免疫球蛋白 G 抗体反应，在第一次免疫开始后第 4 周和第 6 周时，在接种疫苗的小鼠的血清中检测到了这种反应。与对照组相比，接种组脾细胞培养物中Thl相关细胞因子（干扰素γ和白细胞介素[IL]12）的量显着增加，Th2相关细胞因子IL-4显着减少。结论：本研究结果表明，这种编码MERS-CoV S1亚基的重组腺病毒疫苗在小鼠体内引发潜在的保护性抗原特异性体液和细胞免疫反应。这项研究展示了一种有前途的疫苗，用于控制和/或预防人类中东呼吸综合征冠状病毒感染。
Background and Aim: Middle East respiratory syndrome coronavirus (MERS-CoV) has rapidly spread throughout the Middle East since its discovery in 2012. The virus poses a significant global public health threat with potentially devastating effects. In this study, a recombinant adenoviral-based vaccine encoding the spike 1 (S1) subunit of the MERS-CoV genome was constructed, and its humoral, and cellular immune responses were evaluated in mice.Materials and Methods: Mice were immunized initially by intramuscular injection and boosted 3 weeks later by intranasal application. Expression of the S1 protein in the lungs and kidneys was detected using conventional polymerase chain reaction (PCR) and immunohistochemistry (IHC) targeting specific regions within the S1 subunit at weeks 3, 4, 5, and 6 after the first vaccination. Antigen-specific humoral and cellular immune responses were evaluated in serum and in cell culture following in vitro stimulation with a specific 9-mer epitope within the Si protein (CYSSLILDY).Results: S1 protein expression was only detected by IHC in the kidneys of the Ad-MERS-S1 group at week 6 from first immunization, and in both lungs and kidneys of Ad-MERS-S1 group by conventional PCR at weeks 3 and 5 post-prime. The vaccine elicited a specific S1-immunoglobulin G antibody response, which was detected in the sera of the vaccinated mice at weeks 4 and 6 from the onset of the first immunization. There was a significant increase in the amount of Thl-related cytokines (interferon-gamma and interleukin [IL] 12), and a significant decrease in the Th2-related cytokine IL-4 in splenocyte cell culture of the vaccinated group compared with the control groups.Conclusion: The results of this study suggest that this recombinant adenovirus vaccine encoding the S1 subunit of MERS-CoV elicits potentially protective antigen-specific humoral and cellular immune responses in mice. This study demonstrates a promising vaccine for the control and/or prevention of MERS-CoV infection in humans.