Li Jixu, Galon Eloiza May, Guo Huanping, Liu Mingming, Li Yongchang, Ji Shengwei, Zafar Iqra, Gao Yang, Zheng Weiqing, Adjou Moumouni Paul Franck, Rizk Mohamed Abdo, Tumwebaze Maria Agnes, Benedicto Byamukama, Ringo Aaron Edmond, Masatani Tatsunori, Xuan Xuenan
State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, China.
College of Agriculture and Animal Husbandry, Qinghai University, Xining, China.
Front Microbiol. 2021 Mar 11;12:619335. doi: 10.3389/fmicb.2021.619335. eCollection 2021.
Toxoplasmosis is a zoonotic parasitic disease caused by the obligate intracellular protozoa , which threatens a range of warm-blooded mammals including humans. To date, it remains a challenge to find safe and effective drug treatment or vaccine against toxoplasmosis. In this study, our results found that the development of a mutant strain based on gene disruption of dense granule protein 9 (gra9) in type II PLK strain decreased parasite replication , severely attenuated virulence in mice, and significantly reduced the formation of cysts in animals. Hence, we developed an immunization scheme to evaluate the protective immunity of the attenuated strain of Δ in type II PLK parasite as a live attenuated vaccine against toxoplasmosis in the mouse model. Δ vaccination-induced full immune responses characterized by significantly high levels of pro-inflammatory cytokine interferon gamma (IFN-γ) and interleukin-12 (IL-12), maintained the high -specific immunoglobulin G (IgG) level, and mixed high IgG1/IgG2a levels. Their levels provided the complete protective immunity which is a combination of cellular and humoral immunity in mouse models against further infections of lethal doses of type I RH, type II PLK wild-type tachyzoites, or type II PLK cysts. Results showed that Δ vaccination proved its immunogenicity and potency conferring 100% protection against acute and chronic challenges. Together, Δ vaccination provided safe and efficient immune protection against challenging parasites, suggesting that :Δ is a potentially promising live attenuated vaccine candidate.
弓形虫病是一种由专性细胞内原生动物引起的人畜共患寄生虫病，它威胁着包括人类在内的一系列温血哺乳动物。迄今为止，寻找安全有效的抗弓形虫病药物治疗方法或疫苗仍然是一项挑战。在本研究中，我们的结果发现，基于II型PLK株致密颗粒蛋白9（gra9）基因破坏构建的突变株，其寄生虫复制能力下降，在小鼠体内毒力严重减弱，并且动物体内囊肿形成显著减少。因此，我们制定了一种免疫方案，以评估II型PLK寄生虫Δ减毒株作为减毒活疫苗在小鼠模型中针对弓形虫病的保护性免疫。Δ疫苗接种诱导了以促炎细胞因子干扰素γ（IFN-γ）和白细胞介素-12（IL-12）水平显著升高为特征的全面免疫反应，维持了高特异性免疫球蛋白G（IgG）水平以及高IgG1/IgG2a混合水平。这些水平提供了完全的保护性免疫，这是小鼠模型中细胞免疫和体液免疫相结合以抵抗致死剂量的I型RH、II型PLK野生型速殖子或II型PLK囊肿进一步感染的结果。结果表明，Δ疫苗接种证明了其免疫原性和效力，可对急性和慢性攻击提供100%的保护。总之，Δ疫苗接种为抵抗具有挑战性的寄生虫提供了安全有效的免疫保护，表明Δ是一种潜在有前景的减毒活疫苗候选物。
