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评价 SAG1 和 MIC3 疫苗鸡尾酒诱导的针对弓形虫的免疫应答。

Evaluation of immune responses induced by SAG1 and MIC3 vaccine cocktails against Toxoplasma gondii.

机构信息

State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, Hubei, PR China.

出版信息

Vet Parasitol. 2012 Jun 8;187(1-2):140-6. doi: 10.1016/j.vetpar.2011.12.007. Epub 2011 Dec 19.

Abstract

The aim of this study was to evaluate the immune responses of a SAG1 and MIC3 vaccine cocktail in BALB/c mice. Ninety-six BALB/c mice were randomly divided into eight groups, including three plasmid DNA vaccine groups (pcDNA-MIC3, pcDNA-SAG1, pcDNA-MIC3+pcDNA-SAG1), three recombinant pseudotype baculovirus vaccine groups (BV-G-MIC3, BV-G-SAG1, BV-G-SAG1+BV-G-MIC3) and two control groups (PBS and BV-G-EGFP). All groups were immunized intramuscularly twice at three-week intervals. The production of anti-Toxoplasma gondii lysate antigen (TLA) antibodies, lymphoproliferation, levels of IFN-γ, IL-4 and IL-10 and the survival time were monitored after vaccination. The results showed that immunization of BALB/c mice with MIC3 and SAG1 vaccines stimulated both the cellular and humoral immune responses with the production of anti-T. gondii TLA antibodies. The vaccine cocktails of pcDNA-MIC3+pcDNA-SAG1 or BV-G-SAG1+BV-G-MIC3 induced significantly higher immunogenicity than a single-gene vaccine (P<0.05). Splenocytes from the immunized mice significantly proliferated in response to the TLA and released interferon (IFN)-γ (P<0.05). However, the levels of IL-4 and IL-10 in the sera of the immunized mice were not significantly different from those of the controls (P>0.05). Immunization with the vaccine cocktail (BV-G-SAG1+BV-G-MIC3) in mice significantly prolonged survival (50%; P<0.05) against a lethal challenge of T. gondii (RH tachyzoites), while all mice in the other immunized groups and control groups died within 20 and 4 days post-infection, respectively. Furthermore, the recombinant pseudotype baculovirus vaccines induced better immunogenicity than the plasmid DNA vaccines (P<0.05). These results suggest that an excellent vector-mediated vaccine cocktail strategy might be used to develop a new generation of vaccines against T. gondii infection.

摘要

本研究旨在评估 SAG1 和 MIC3 疫苗鸡尾酒在 BALB/c 小鼠中的免疫应答。96 只 BALB/c 小鼠被随机分为 8 组,包括 3 个质粒 DNA 疫苗组(pcDNA-MIC3、pcDNA-SAG1、pcDNA-MIC3+pcDNA-SAG1)、3 个重组假型杆状病毒疫苗组(BV-G-MIC3、BV-G-SAG1、BV-G-SAG1+BV-G-MIC3)和 2 个对照组(PBS 和 BV-G-EGFP)。所有组均在 3 周间隔内肌肉内免疫 2 次。在接种后监测抗弓形虫裂解抗原(TLA)抗体的产生、淋巴细胞增殖、IFN-γ、IL-4 和 IL-10 的水平以及存活时间。结果表明,用 MIC3 和 SAG1 疫苗免疫 BALB/c 小鼠可刺激细胞和体液免疫应答,产生抗弓形虫 TLA 抗体。pcDNA-MIC3+pcDNA-SAG1 或 BV-G-SAG1+BV-G-MIC3 疫苗鸡尾酒诱导的免疫原性明显高于单基因疫苗(P<0.05)。免疫小鼠的脾细胞对 TLA 显著增殖,并释放干扰素(IFN)-γ(P<0.05)。然而,免疫小鼠血清中 IL-4 和 IL-10 的水平与对照组无显著差异(P>0.05)。用疫苗鸡尾酒(BV-G-SAG1+BV-G-MIC3)免疫小鼠可显著延长对致死性弓形虫(RH 速殖子)攻击的存活时间(50%;P<0.05),而其他免疫组和对照组的所有小鼠分别在感染后 20 天和 4 天内死亡。此外,重组假型杆状病毒疫苗诱导的免疫原性优于质粒 DNA 疫苗(P<0.05)。这些结果表明,一种优秀的载体介导的疫苗鸡尾酒策略可能被用于开发新一代弓形虫感染疫苗。

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