Deletion of Toxoplasma Rhoptry Protein 38 (PruΔrop38) as a Vaccine Candidate for Toxoplasmosis in a Murine Model.

Deletion of Toxoplasma Rhoptry Protein 38 (PruΔrop38) as a Vaccine Candidate for Toxoplasmosis in a Murine Model.
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删除弓形虫 Rhoptry 蛋白 38 (PruÎrop38) 作为小鼠模型中弓形虫病的候选疫苗

DOI:
10.3390/biomedicines10061336
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发表时间:
2022-06-06
期刊:
影响因子:
4.7
通讯作者:
--
中科院分区:
工程技术3区
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--
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弓形虫病是一种严重威胁人类和动物健康的人畜共患传染病。本研究通过弓形虫棒状体蛋白38(PruΔ rop 38)缺失对小鼠的致病性和免疫保护性评价其疫苗潜力。腹腔接种1 × 103、2 × 103、4 × 103株PruΔ rop 38的小鼠无明显体征,而接种1 × 103株Pru亲本株的小鼠出现明显消瘦和驼背,提示PruΔ rop 38对小鼠的致病性明显降低。1 × 102 PruΔ rop 38疫苗接种引发混合Th 1/Th 2应答(Th 1应答占主导地位),从第3周至第12周血清中IgG、IgG 2a和IgG 1水平较高,免疫后30或60天脾细胞悬液中IFN-γ、IL-12和IL-10显著升高。所有接种疫苗的小鼠在腹腔内感染速殖子(RH、Pru、VEG或TgcatBJ 1)或经口感染包囊(Pru或ME 49)时均存活。在接种疫苗的小鼠中,Pru速殖子、Pru包囊和ME 49包囊攻击期间的脑寄生虫负荷显著降低。免疫持续时间表明,PruΔ rop 38疫苗对不同基因型弓形虫株不同感染途径的攻击均有保护作用。总的来说,这些发现表明PruΔ rop 38是一种减毒株,可对小鼠急性或慢性弓形虫病提供长期保护作用。
Toxoplasmosis is a serious zoonotic disease that threatens human and animal health. Here, we evaluated the vaccine potential of the deletion of Toxoplasma rhoptry protein 38 (PruΔrop38) through its pathogenicity and immunoprotective efficacy in mice. Mice inoculated intraperitoneally with 1 × 103, 2 × 103, or 4 × 103 PruΔrop38 showed no visible signs, whereas mice inoculated with 1 × 103 parental Pru strain showed obvious wasting and bow-back, suggesting a significantly lower pathogenicity of PruΔrop38 in mice. Vaccination with 1 × 102 PruΔrop38 triggered a mixed Th1/Th2 response (Th1 response predominant), with higher IgG, IgG2a, and IgG1 levels in serum from week 3 to week 12, and a significant increase in IFN-γ, IL-12, and IL-10 in suspensions of splenocytes at 30 or 60 days post-immunization. All vaccinated mice survived when infected intraperitoneally with tachyzoites (RH, Pru, VEG, or TgcatBJ1) or when infected orally with cysts (Pru or ME49). The brain parasite burden during Pru tachyzoite, Pru cyst and ME49 cyst challenges were significantly reduced in vaccinated mice. The duration of immunization showed that vaccination with PruΔrop38 could protect mice from challenge with different varied genotypes of Toxoplasma strains against different routes of infection. Collectively, these findings indicate that PruΔrop38 is an attenuated strain that provides long-term protective efficacy against acute or chronic toxoplasmosis in mice.
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