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首页> 外文期刊>Infection and immunity >Nonreplicating, Cyst-Defective Type II Toxoplasma gondii Vaccine Strains Stimulate Protective Immunity against Acute and Chronic Infection
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Nonreplicating, Cyst-Defective Type II Toxoplasma gondii Vaccine Strains Stimulate Protective Immunity against Acute and Chronic Infection

机译：非复制，囊肿缺陷型II型弓形虫疫苗株刺激针对急性和慢性感染的保护性免疫。

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Live attenuated vaccine strains, such as type I nonreplicating uracil auxotroph mutants, are highly effective in eliciting lifelong immunity to virulent acute infection by Toxoplasma gondii. However, it is currently unknown whether vaccine-elicited immunity can provide protection against acute infection and also prevent chronic infection. To address this problem, we developed nonreverting, nonreplicating, live attenuated uracil auxotroph vaccine strains in the type II Δku80 genetic background by targeting the deletion of the orotidine 5′-monophosphate decarboxylase (OMPDC) and uridine phosphorylase (UP) genes. Deletion of OMPDC induced a severe uracil auxotrophy with loss of replication, loss of virulence in mice, and loss of the ability to develop cysts and chronic infection. Vaccination of mice using type II Δku80 Δompdc mutants stimulated a fully protective CD8+ T cell-dependent immunity that prevented acute infection by type I and type II strains of T. gondii, and this vaccination also severely reduced or prevented cyst formation after type II challenge infection. Nonreverting, nonreplicating, and non-cyst-forming Δompdc mutants provide new tools to examine protective immune responses elicited by vaccination with a live attenuated type II vaccine.
机译：减毒活疫苗株，例如非复制型I型尿嘧啶营养缺陷型突变株，在引发针对弓形虫强烈急性感染的终生免疫方面非常有效。但是，目前尚不知道疫苗引发的免疫能否提供针对急性感染的保护作用并预防慢性感染。为解决这个问题，我们针对II型Δ ku80 遗传背景开发了一种不可逆，不可复制的减毒活型尿嘧啶营养缺陷型疫苗株，其靶向靶向是删除了奥罗替丁5'-单磷酸脱羧酶（ OMPDC < / em>）和尿苷磷酸化酶（ UP ）基因。删除 OMPDC 会导致严重的尿嘧啶营养缺陷，导致复制能力丧失，小鼠毒性降低，囊肿形成和慢性感染能力下降。使用II型Δ ku80 Δ ompdc 突变体对小鼠进行疫苗接种可激发完全保护性的CD8 + T细胞依赖性免疫，从而防止I型急性感染和刚地弓形虫的II型毒株，这种疫苗接种还能严重减少或防止II型攻击性感染后的囊肿形成。非还原，非复制和非囊肿性Δ ompdc 突变体提供了新的工具，可用于检查通过减毒活疫苗接种引起的保护性免疫应答。

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