Xie Shi-Chen, Lv Yi-Han, Wang Meng, Zheng Xiao-Nan, Wang Jin-Lei, Fu Bao-Quan, Zhu Xing-Quan
State Key Laboratory for Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province 730046, People's Republic of China; Laboratory of Parasitic Diseases, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi Province 030801, People's Republic of China.
Laboratory of Parasitic Diseases, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi Province 030801, People's Republic of China.
Int J Parasitol. 2025 Aug 7. doi: 10.1016/j.ijpara.2025.08.002.
Toxoplasma gondii is a zoonotic protozoan pathogen capable of infecting humans and nearly all warm-blooded animals, and causing substantial economic losses to the livestock industry. Developing an effective vaccine against T. gondii remains an urgent priority for controlling the spread of this zoonotic parasite. In this study, we evaluated the protective efficacy of a live-attenuated T. gondii PruΔpp2a-c mutant in both mice and cats. Immunization with PruΔpp2a-c elicited strong cellular (IL-2, IL-4, IL-10, IL-12, and IFN-γ) and humoral (IgG, IgG1, and IgG2a) immune responses in mice, conferring protection against lethal challenge with various T. gondii strains, including highly virulent Type I (RH), mildly virulent ToxoDB#9 (PYS), and less virulent Type II (Pru) strains. While partial protection was observed against virulent strains, almost complete immune protection was achieved against both acute and chronic infections by the less virulent Pru strain, along with a significant reduction in brain cyst burden (P < 0.001). Notably, vaccination of cats with PruΔpp2a-c induced high antibody titers and led to a 94.5 % reduction in fecal oocyst shedding (P < 0.001) following homologous challenge, thereby significantly decreasing the potential for environmental transmission. These findings demonstrate that PruΔpp2a-c provides strong cross-protection against various T. gondii strains and substantially limits oocyst shedding. The dual efficacy observed in both intermediate and definitive hosts highlights PruΔpp2a-c as a promising live-attenuated vaccine candidate for preventing transmission of T. gondii by cats.
刚地弓形虫是一种人畜共患的原生动物病原体，能够感染人类和几乎所有温血动物，并给畜牧业造成重大经济损失。开发一种有效的抗刚地弓形虫疫苗仍然是控制这种人畜共患寄生虫传播的当务之急。在本研究中，我们评估了减毒活刚地弓形虫PruΔpp2a - c突变体在小鼠和猫体内的保护效力。用PruΔpp2a - c免疫在小鼠中引发了强烈的细胞免疫（IL - 2、IL - 4、IL - 10、IL - 12和IFN - γ）和体液免疫（IgG、IgG1和IgG2a）反应，使其对包括高毒力I型（RH）、中等毒力ToxoDB#9（PYS）和低毒力II型（Pru）菌株在内的各种刚地弓形虫菌株的致死性攻击具有保护作用。虽然观察到对强毒株有部分保护作用，但对低毒力Pru菌株的急性和慢性感染几乎实现了完全免疫保护，同时脑囊肿负担显著降低（P < 0.001）。值得注意的是，用PruΔpp2a - c对猫进行疫苗接种可诱导高抗体滴度，并在同源攻击后使粪便中卵囊排出量减少94.5%（P < 0.001），从而显著降低环境传播的可能性。这些发现表明，PruΔpp2a - c对各种刚地弓形虫菌株具有强大的交叉保护作用，并能大幅限制卵囊排出。在中间宿主和终末宿主中观察到的双重效力突出了PruΔpp2a - c作为一种有前景的减毒活疫苗候选物，可用于预防猫传播刚地弓形虫。
