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Abstract：
Mycoplasma hyopneumoniae (M. hyopneumoniae, Mhp) is the etiological agent of swine enzootic pneumonia (EP), which has been associated with considerable economic losses due to reduced daily weight gain and feed efficiency. Adhesion to the cilia is important for Mhp to colonize the respiratory epithelium. Therefore, a successful vaccine must induce broad Mhp-specific immune responses at the mucosal surface. Recombinant attenuated Salmonella strains are believed to act as powerful live vaccine vectors that are able to elicit mucosal immune responses against various pathogens. To develop efficacious and inexpensive vaccines against Mhp, the immune responses and protection induced by recombinant attenuated Salmonella vaccines based on the P42 and P97 antigens of Mhp were evaluated. In general, the oral inoculation of recombinant rSC0016(pS-P42) or rSC0016(pS-P97) resulted in strong mucosal immunity, cell-mediated immunity, and humoral immunity, which was a mixed Th1/Th2-type response. In addition, the levels of specific IL-4 and IFN-γ in the immunized mice were increased, and the proliferation of lymphocytes was also enhanced, confirming the production of a good cellular immune response. Finally, both vaccine candidate strains were able to improve the weight loss of mice after a challenge and reduce clinical symptoms, lung pathological damage, and the inflammatory cell infiltration. These results suggest that the delivery of protective antigens with recombinant attenuated Salmonella vectors may be an effective means by which to combat Mhp infection. IMPORTANCE Mhp is the main pathogen of porcine enzootic pneumonia, a highly infectious and economically significant respiratory disease that affects pigs of all ages. As the target tissue of Mhp infections are the mucosal sites of the respiratory tract, the induction of protective immunity at the mucosal tissues is the most efficient strategy by which to block disease transmission. Because the stimulation of mucosal immune responses is efficient, Salmonella-vector oral vaccines are expected to be especially useful against mucosal-invading pathogens. In this study, we expressed the immunogenic proteins of P42 and P97 with the attenuated Salmonella Choleraesuis vector rSC0016, thereby generating a low-cost and more effective vaccine candidate against Mhp by inducing significant mucosal, humoral and cellular immunity. Furthermore, rSC0016(pS-P42) effectively prevents Mhp-induced weight loss and the pulmonary inflammation of mice. Because of the effectiveness of rSC0016(pS-P42) against Mhp infection in mice, this novel vaccine candidate strain shows great potential for its use in the pig breeding industry.
摘要：
猪肺炎支原体（M.猪肺炎,Mhp）是猪地方性肺炎（EP）的病原体，由于每日增重和饲料效率降低，这与相当大的经济损失有关。对纤毛的粘附对于Mhp定植于呼吸上皮是重要的。因此,成功的疫苗必须在粘膜表面诱导广泛的Mhp特异性免疫应答。重组减毒沙门氏菌菌株被认为是强大的活疫苗载体,其能够引发针对各种病原体的粘膜免疫应答。为了开发针对Mhp的有效且廉价的疫苗，评价了基于Mhp的P42和P97抗原的重组减毒沙门氏菌疫苗诱导的免疫应答和保护作用。总的来说,口服接种重组rSC0016(pS-P42)或rSC0016(pS-P97)导致强烈的粘膜免疫,细胞介导的免疫，和体液免疫,这是混合的Th1/Th2型反应。此外,免疫小鼠体内特异性IL-4和IFN-γ水平升高,淋巴细胞的增殖也增强了，确认产生良好的细胞免疫反应。最后,两种疫苗候选株都能够改善攻击后小鼠的体重减轻并减轻临床症状，肺病理损伤，和炎症细胞浸润。这些结果表明，用重组减毒沙门氏菌载体递送保护性抗原可能是对抗Mhp感染的有效手段。重要性Mhp是猪地方性肺炎的主要病原体,一种高度传染性和经济意义重大的呼吸道疾病，影响所有年龄的猪。由于Mhp感染的靶组织是呼吸道的粘膜部位，在粘膜组织诱导保护性免疫是阻断疾病传播的最有效策略。因为刺激粘膜免疫反应是有效的，沙门氏菌载体口服疫苗预计对粘膜侵入病原体特别有用。在这项研究中,我们用减毒的霍乱沙门氏菌载体rSC0016表达了P42和P97的免疫原性蛋白，从而通过诱导显著的粘膜，产生了一种低成本和更有效的Mhp疫苗候选物，体液和细胞免疫。此外，rSC0016(pS-P42)有效预防Mhp诱导的小鼠体重减轻和肺部炎症。由于rSC0016（pS-P42）对小鼠Mhp感染的有效性，这种新型疫苗候选菌株在猪养殖业中显示出巨大的应用潜力。
