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编码刚地弓形虫延伸因子1-α的DNA疫苗诱导BALB/c小鼠对急性弓形虫病的保护性免疫

Protective immunity against acute toxoplasmosis in BALB/c mice induced by a DNA vaccine encoding Toxoplasma gondii elongation factor 1-alpha.

作者信息

Wang Shuai, Wang YuJian, Sun XiaoNi, Zhang ZhenChao, Liu TingQi, Gadahi Javaid Ali, Hassan Ibrahim Adam, Xu LiXin, Yan RuoFeng, Song XiaoKai, Li XiangRui

机构信息

College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, PR China.

出版信息

BMC Infect Dis. 2015 Oct 24;15:448. doi: 10.1186/s12879-015-1220-5.

Abstract

BACKGROUND

Toxoplasma gondii can infect almost all warm-blood animals including human beings. The high incidence and severe damage that can be caused by T. gondii infection clearly indicates the need for the development of a vaccine. T. gondii elongation factor 1-alpha (TgEF-1α) plays an important role in pathogenesis and host cell invasion for this parasite. The aim of this study was to evaluate the immune protective efficacy of a DNA vaccine encoding TgEF-1α gene against acute T. gondii infection in mice.

METHODS

A DNA vaccine (pVAX-EF-1α) encoding T. gondii EF-1a (TgEF-1α) gene was constructed and its immune response and protective efficacy against lethal challenge in BALB/c mice were evaluated.

RESULTS

Mice inoculated with the pVAX-EF-1α vaccine had a high level of specific anti-T. gondii antibodies and produced high levels of IFN-gamma, interleukin (IL)-4, and IL-17. The expression levels of MHC-I and MHC-II molecules as well as the percentages of both CD4(+) and CD8(+) T cells in mice vaccinated with pVAX-EF-1α were significantly increased (p < 0.05), compared with those in all the mice from control groups (blank control, PBS, and pVAXI). Immunization with pVAX-EF-1α significantly (p < 0.05) prolonged mouse survival time to 14.1 ± 1.7 days after challenge infection with the virulent T. gondii RH strain, compared with mice in the control groups which died within 8 days.

CONCLUSIONS

DNA vaccination with pVAX-EF-1α triggered strong humoral and cellular responses and induced effective protection in mice against acute T. gondii infection, indicating that TgEF-1α is a promising vaccine candidate against acute toxoplasmosis.

摘要

背景

刚地弓形虫可感染包括人类在内的几乎所有温血动物。刚地弓形虫感染所致的高发病率和严重损害清楚表明需要研发疫苗。刚地弓形虫延伸因子1-α(TgEF-1α)在该寄生虫的发病机制和宿主细胞侵袭中起重要作用。本研究旨在评估编码TgEF-1α基因的DNA疫苗对小鼠急性刚地弓形虫感染的免疫保护效果。

方法

构建编码刚地弓形虫EF-1a(TgEF-1α)基因的DNA疫苗(pVAX-EF-1α),并评估其对BALB/c小鼠致死性攻击的免疫反应和保护效果。

结果

接种pVAX-EF-1α疫苗的小鼠具有高水平的特异性抗刚地弓形虫抗体,并产生高水平的干扰素-γ、白细胞介素(IL)-4和IL-17。与对照组(空白对照、PBS和pVAXI)的所有小鼠相比,接种pVAX-EF-1α的小鼠中MHC-I和MHC-II分子的表达水平以及CD4(+)和CD8(+) T细胞的百分比均显著增加(p < 0.05)。与对照组在8天内死亡的小鼠相比,用pVAX-EF-1α免疫显著(p < 0.05)延长了小鼠在感染强毒株刚地弓形虫RH株后的存活时间至14.1±1.7天。

结论

用pVAX-EF-1α进行DNA疫苗接种引发了强烈的体液和细胞反应,并在小鼠中诱导了针对急性刚地弓形虫感染的有效保护,表明TgEF-1α是一种有前景的抗急性弓形虫病疫苗候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d32f/4619988/7e7229a20e93/12879_2015_1220_Fig1_HTML.jpg

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