Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, United States of America.
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, United States of America.
PLoS One. 2024 Apr 29;19(4):e0302555. doi: 10.1371/journal.pone.0302555. eCollection 2024.
Clostridial dermatitis (CD), caused by Clostridium septicum, is an emerging disease of increasing economic importance in turkeys. Currently, there are no effective vaccines for CD control. Here, two non-toxic domains of C. septicum alpha toxin, namely ntATX-D1 and ntATX-D2, were identified, cloned, and expressed in Escherichia coli as recombinant subunit proteins to investigate their use as potential vaccine candidates. Experimental groups consisted of a Negative control (NCx) that did not receive C. septicum challenge, while the adjuvant-only Positive control (PCx), ntATX-D1 immunization (D1) and ntATX-D2 immunization (D2) groups received C. septicum challenge. Turkeys were immunized subcutaneously with 100 μg of protein at 7, 8 and 9 weeks of age along with an oil-in-water nano-emulsion adjuvant, followed by C. septicum challenge at 11 weeks of age. Results showed that while 46.2% of birds in the PCx group died post-challenge, the rate of mortality in D1- or D2-immunization groups was 13.3%. The gross and histopathological lesions in the skin, muscle and spleen showed that the disease severity was highest in PCx group, while the D2-immunized birds had significantly lower lesion scores when compared to PCx. Gene expression analysis revealed that PCx birds had significantly higher expression of pro-inflammatory cytokine genes in the skin, muscle and spleen than the NCx group, while the D2 group had significantly lower expression of these genes compared to PCx. Peripheral blood cellular analysis showed increased frequencies of activated CD4+ and/or CD8+ cells in the D1 and D2-immunized groups. Additionally, the immunized turkeys developed antigen-specific serum IgY antibodies. Collectively, these findings indicate that ntATX proteins, specifically the ntATX-D2 can be a promising vaccine candidate for protecting turkeys against CD and that the protection mechanisms may include downregulation of C. septicum-induced inflammation and increased CD4+ and CD8+ cellular activation.
梭菌性皮炎（CD）是由梭状芽孢杆菌引起的一种新兴疾病，在火鸡中具有日益重要的经济意义。目前，尚无针对 CD 的有效疫苗。在这里，我们鉴定、克隆并在大肠杆菌中表达了两种无毒的梭状芽孢杆菌α毒素结构域，即 ntATX-D1 和 ntATX-D2，以研究它们作为潜在疫苗候选物的用途。实验组包括未接受梭状芽孢杆菌挑战的阴性对照（NCx），而仅用佐剂的阳性对照（PCx）、ntATX-D1 免疫（D1）和 ntATX-D2 免疫（D2）组接受梭状芽孢杆菌挑战。火鸡在 7、8 和 9 周龄时，每只皮下免疫 100μg 蛋白和油水纳米乳液佐剂，然后在 11 周龄时接受梭状芽孢杆菌挑战。结果表明，PCx 组 46.2%的鸟类在挑战后死亡，而 D1 或 D2 免疫组的死亡率为 13.3%。皮肤、肌肉和脾脏的大体和组织病理学病变表明，PCx 组的疾病严重程度最高，而 D2 免疫组的病变评分明显低于 PCx 组。基因表达分析表明，与 NCx 组相比，PCx 组鸟类皮肤、肌肉和脾脏中促炎细胞因子基因的表达显著升高，而 D2 组这些基因的表达明显低于 PCx 组。外周血细胞分析表明，D1 和 D2 免疫组的活化 CD4+和/或 CD8+细胞频率增加。此外，免疫火鸡产生了针对抗原的血清 IgY 抗体。综上所述，这些结果表明，ntATX 蛋白，特别是 ntATX-D2，可能是一种有前途的疫苗候选物，可用于保护火鸡免受 CD 的侵害，其保护机制可能包括下调梭状芽孢杆菌诱导的炎症和增加 CD4+和 CD8+细胞的活化。
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