Safety and protective efficacy of Salmonella Pullorum spiC and rfaH deletion rough mutant as a live attenuated DIVA vaccine candidate.
Safety and protective efficacy of Salmonella Pullorum spiC and rfaH deletion rough mutant as a live attenuated DIVA vaccine candidate.
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鸡白痢沙门氏菌 spiC 和 rfaH 缺失粗突变体作为 DIVA 减毒活疫苗候选物的安全性和保护功效
DOI：
10.1016/j.psj.2021.101655
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发表时间：
2022-03
期刊：
影响因子：
4.4
通讯作者：
Pan Z
中科院分区：
文献类型：
--
作者：
Kang X;Yang Y;Meng C;Wang X;Liu B;Geng S;Jiao X;Pan Z
鸡白痢沙门氏菌（S.鸡白痢（Pullorum）引起鸡白痢病（PD），这是一种急性全身性疾病，由于其在雏鸡中的高发病率和死亡率，在许多发展中国家导致严重的经济损失。减毒活疫苗被认为是控制沙门氏菌感染的有效措施。此外，DIVA（区分感染动物和接种动物）特征不受沙门氏菌感染的血清学监测的干扰是沙门氏菌疫苗开发中的重要考虑因素。在本研究中，我们评估了S.粗糙白痢突变体S06004ΔspiCΔrfaH作为鸡中的活减毒DIVA疫苗候选物。S06004ΔspiCΔrfaH表现出显著的粗脂多糖（LPS）表型，其与吖啶黄素凝集，而不与O9单抗凝集。与野生型相比，粗糙突变体的50%致死剂量（LD 50）增加了100倍，证实了其减毒作用。突变菌株还显示脾和肝中的细菌定殖减少。用突变株免疫对体重没有影响，在肝脏和脾脏中没有观察到组织损伤。S.血清中的鸡白痢特异性IgG滴度表明免疫组诱导了显著的体液免疫应答。细胞免疫反应还通过分析脾脏中淋巴细胞增殖和细胞因子表达来引起。此外，S06004ΔspiCΔrfaH免疫组的血清学试验呈阴性反应，而野生型S06004感染组的血清学试验呈强阳性，显示DIVA能力。经肌肉注射攻毒后，免疫鸡的存活率为87%。而对照组的成活率为20%。总体而言，这些结果表明，粗糙突变株S06004ΔspiCΔrfaH菌株可开发为有效的减毒活DIVA疫苗候选菌株，以控制全身性S.鸡白痢感染不受沙门氏菌病监测程序的干扰。
Salmonella enterica serovar Pullorum (S. Pullorum) causes pullorum disease (PD), which is an acute systemic disease, in chickens, and leads to serious economic losses in many developing countries because of its high morbidity and mortality rate in young chicks. The live-attenuated vaccine is considered to be an effective measure to control the Salmonella infection. In addition, the DIVA (differentiation of infected and vaccinated animals) feature without the interference of serological monitoring of Salmonella infection is an important consideration in the development of the Salmonella vaccine. In this study, we evaluated the immunogenicity and protective efficacy of a S. Pullorum rough mutant S06004ΔspiCΔrfaH as a live attenuated DIVA vaccine candidate in chickens. The S06004ΔspiCΔrfaH exhibited a significant rough lipopolysaccharides (LPS) phenotype which was agglutinated with the acriflavine, not with the O9 mono antibody. Compared to the wild-type, 50% lethal dose (LD50) of the rough mutant increased 100-fold confirmed its attenuation. The mutant strain also showed a decreased bacterial colonization in the spleen and liver. The immunization with the mutant strain had no effect on the body weight and no tissue lesions were observed in the liver and spleen. The high level of the S. Pullorum-specific IgG titers in the serum indicated that significant humoral immune responses were induced in the immunization group. The cellular immune responses were also elicited from the analysis of lymphocyte proliferation and expression of cytokines in the spleen. In addition, the S06004ΔspiCΔrfaH immunized group exhibited a negative response for the serological test, while the wild-type S06004 infection group was strongly positive for the serological test showing a DIVA capability. The survival rates in the vaccinated chickens were 87% after intramuscular challenge with wild-type S. Pullorum, while the survival rates were 20% in the control groups. Overall, these results have demonstrated that the rough mutant S06004ΔspiCΔrfaH strain can be developed as an efficient live attenuated DIVA vaccine candidate to control the systemic S. Pullorum infection without the interference of salmonellosis monitoring program in poultry.
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