Imhof Dennis, Pownall William Robert, Monney Camille, Oevermann Anna, Hemphill Andrew
Institute of Parasitology, Vetsuisse Faculty, University of Bern, Länggassstrasse 122, 3012 Bern, Switzerland.
Graduate School for Cellular and Biomedical Sciences, University of Bern, Mittelstrasse 43, 3012 Bern, Switzerland.
Vaccines (Basel). 2021 Nov 26;9(12):1400. doi: 10.3390/vaccines9121400.
The apicomplexan parasite is the worldwide leading cause of abortion and stillbirth in cattle. An attenuated mutant strain (Lm3Dx) was engineered by deleting the virulence genes , , and in order to avoid systemic infection and to target the vector to antigen-presenting cells (APCs). Insertion of , coding for the major surface protein NcSAG1 of , yielded the vaccine strain Lm3Dx_NcSAG1. The efficacy of Lm3Dx_NcSAG1 was assessed by inoculating 1 × 10, 1 × 10, or 1 × 10 CFU of Lm3Dx_NcSAG1 into female BALB/c mice by intramuscular injection three times at two-week intervals, and subsequent challenge with 1 × 10 tachyzoites of the highly virulent NcSpain-7 strain on day 7 of pregnancy. Dose-dependent protective effects were seen, with a postnatal offspring survival rate of 67% in the group treated with 1 × 10 CFU of Lm3Dx_NcSAG1 compared to 5% survival in the non-vaccinated control group. At euthanasia (25 days post-partum), IgG antibody titers were significantly decreased in the groups receiving the two higher doses and cytokines recall responses in splenocyte culture supernatants (IFN-γ, IL-4, and IL-10) were increased in the vaccinated groups. Thus, Lm3Dx_NcSAG1 induces immune-protective effects associated with a balanced Th1/Th2 response in a pregnant neosporosis mouse model and should be further assessed in ruminant models.
顶复门寄生虫是全球范围内牛流产和死产的主要原因。为了避免全身感染并使载体靶向抗原呈递细胞（APC），通过删除毒力基因、和构建了一种减毒突变株（Lm3Dx）。插入编码主要表面蛋白NcSAG1的，产生了疫苗株Lm3Dx_NcSAG1。通过以两周的间隔肌肉注射三次1×10、1×10或1×10 CFU的Lm3Dx_NcSAG1接种雌性BALB/c小鼠，随后在怀孕第7天用1×10高毒力NcSpain-7株速殖子进行攻击，评估Lm3Dx_NcSAG1的功效。观察到剂量依赖性保护作用，与未接种疫苗的对照组5%的存活率相比，用1×10 CFU的Lm3Dx_NcSAG1处理的组产后后代存活率为67%。在安乐死时（产后25天），接受两个较高剂量的组中IgG抗体滴度显著降低，接种疫苗组脾细胞培养上清液中的细胞因子回忆反应（IFN-γ、IL-4和IL-10）增加。因此，Lm3Dx_NcSAG1在怀孕的新孢子虫病小鼠模型中诱导与平衡的Th1/Th2反应相关的免疫保护作用，应在反刍动物模型中进一步评估。
