Mic1-3 knockout of Toxoplasma gondii is a successful vaccine against chronic and congenital toxoplasmosis in mice
Mic1-3 knockout of Toxoplasma gondii is a successful vaccine against chronic and congenital toxoplasmosis in mice
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DOI：
10.1086/507706
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发表时间：
2006-10-15
影响因子：
6.4
通讯作者：
Mevelec, Marie-Noelle
中科院分区：
文献类型：
--
作者：
Ismael, Alaa Bassuny;Dimier-Poisson, Isabelle;Mevelec, Marie-Noelle
背景。我们评估了一种新的疫苗Mic1-3KO对小鼠慢性和先天性弓形虫病的疗效。mic1 - 3ko是一种缺乏mic1和mic3基因的弓形虫RH突变株。用Mic1-3KO速殖子接种OF1小鼠，并口服刚地弓形虫（菌株76K）。评估了免疫应答和对慢性感染（脑组织囊肿负荷）和先天性感染（母胎传播、存活率、体重和幼崽慢性感染）的保护作用。Mic1-3KO诱导了强烈的体液和细胞T辅助（Th） 1反应，并对慢性感染具有高度显著的保护作用（脑组织囊肿减少96%）。在接种疫苗的母鼠中，怀孕期间感染的感染胎儿少于未接种疫苗的母鼠（4.6% vs. 33.3%）。所有在接种过疫苗的大坝出生的幼崽都存活了下来，并且与未接种过疫苗的大坝出生的幼崽体重相同。此外，与未接种疫苗的感染母鼠相比，它们脑组织中的囊肿明显减少（约91%）。在怀孕期间，预防先天性疾病与白细胞介素-10调节的细胞Th1反应有关。分娩1个月后，接种疫苗的感染母鼠脑组织囊肿比未接种疫苗的感染母鼠少96%。Mic1-3KO是一种有效的慢性和先天性弓形虫病疫苗。
Background. We evaluated a new vaccine, Mic1-3KO, against both chronic and congenital toxoplasmosis in mice. Mic1-3KO is a mutant strain of Toxoplasma gondii RH that lacks the mic1 and mic3 genes.Methods. OF1 mice were vaccinated with Mic1-3KO tachyzoites and challenged orally with T. gondii (strain 76K). Immune responses and protection against chronic infection (cyst load in brain tissue) and congenital infection (maternofetal transmission, survival, body weight, and chronic infection in pups) were evaluated.Results. Mic1-3KO induced a strong humoral and cellular T helper (Th) 1 response and conferred highly significant protection against chronic infection (> 96% reduction in cysts in brain tissue). Fewer infected fetuses were observed in vaccinated dams that were infected during pregnancy than in nonvaccinated infected dams (4.6% vs. 33.3%). All pups born to vaccinated infected dams survived and had the same weight as those born to nonvaccinated uninfected dams. Furthermore, they had significantly fewer cysts in brain tissue (> 91%) than pups from nonvaccinated infected dams. During pregnancy, protection against congenital disease was associated with a cellular Th1 response regulated by interleukin-10. One month after delivery, vaccinated infected dams had > 96% fewer cysts in their brain tissue than nonvaccinated infected dams.Conclusion. Mic1-3KO is an effective vaccine against chronic and congenital toxoplasmosis.