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构建和评估基孔肯雅病毒重组腺病毒候选疫苗。

Construction and Evaluation of Recombinant Adenovirus Candidate Vaccines for Chikungunya Virus.

机构信息

College of Laboratory, Jilin Medical University, Jilin 132013, China.

Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130117, China.

出版信息

Viruses. 2022 Aug 15;14(8):1779. doi: 10.3390/v14081779.

Abstract

Chikungunya virus (CHIKV) is a mosquito-borne virus. The emergence of CHIKV infection has raised global concern, and there is a growing need to develop safe and effective vaccines. Here, adenovirus 5 was used as the vaccine vector to construct recombinant adenoviruses expressing CHIKV E2, E1, and E2-6K-E1, respectively. And then the immunogenicity and protective efficiency against CHIKV were evaluated in BALB/c mice. Compared to the ad-wt control group, all three vaccines elicited significant humoral and cellar immune responses. The levels of neutralizing antibodies in the rAd-CHIKV-E2-6K-E1 and rAd-CHIKV-E2 groups both reached 1:256, which were 3.2 times higher than those in the rAd-CHIKV-E1 group. Furthermore, the levels of lymphocyte proliferation in rAd-CHIKV-E2-6K-E1 group were the highest. Besides, the concentrations of IFN-γ and IL-4 in mice immunized with rAd-CHIKV-E2-6K-E1 were 1.37 and 1.20 times higher than those in ad-wt immunized mice, respectively. After the challenge, mice in the rAd-CHIKV-E2-6K-E1 and rAd-CHIKV-E2 groups lost 2% of their body weight compared with 5% in the ad-wt control group. And low viral loads were detected in the heart, kidney, and blood of mice immunized with rAd-CHIKV-E2-6K-E1 and rAd-CHIKV-E2 at 3-5 dpc, which decreased by 0.4-0.7 orders of magnitude compared with the ad-wt control. Overall, these data suggest that the recombinant adenovirus is a potential candidate vaccine against CHIKV.

摘要

基孔肯雅病毒(CHIKV)是一种通过蚊子传播的病毒。CHIKV 感染的出现引起了全球关注,因此迫切需要开发安全有效的疫苗。在这里,我们使用腺病毒 5 作为疫苗载体,构建了分别表达 CHIKV E2、E1 和 E2-6K-E1 的重组腺病毒。然后,在 BALB/c 小鼠中评估了它们针对 CHIKV 的免疫原性和保护效率。与 ad-wt 对照组相比,所有三种疫苗都引起了明显的体液和细胞免疫应答。rAd-CHIKV-E2-6K-E1 和 rAd-CHIKV-E2 组的中和抗体水平均达到 1:256,比 rAd-CHIKV-E1 组高 3.2 倍。此外,rAd-CHIKV-E2-6K-E1 组的淋巴细胞增殖水平最高。此外,rAd-CHIKV-E2-6K-E1 免疫的小鼠中 IFN-γ 和 IL-4 的浓度分别比 ad-wt 免疫的小鼠高 1.37 倍和 1.20 倍。攻毒后,rAd-CHIKV-E2-6K-E1 和 rAd-CHIKV-E2 组的小鼠体重减轻 2%,而 ad-wt 对照组的小鼠体重减轻 5%。在 3-5 dpc,rAd-CHIKV-E2-6K-E1 和 rAd-CHIKV-E2 免疫的小鼠心脏、肾脏和血液中的病毒载量分别降低了 0.4-0.7 个数量级,与 ad-wt 对照组相比。总的来说,这些数据表明重组腺病毒是一种有潜力的 CHIKV 候选疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b07a/9414632/233e76fc8832/viruses-14-01779-g001.jpg

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