Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL 32608, USA.
College of Animal Science and Technology, Southwest University, Chongqing 400715, China.
Vaccine. 2018 Feb 14;36(8):1038-1046. doi: 10.1016/j.vaccine.2018.01.036. Epub 2018 Jan 19.
Avian pathogenic Escherichia coli (APEC), a leading cause of avian airsacculitis and colibacillosis, is responsible for significant economic loss in the poultry industry. APEC serogroups O1, O2, and O78 are predominantly associated with disease. Lipopolysaccharide (LPS) O-antigen has been shown to be a potent antigen for inducing specific protective immune responses. Therefore, we sought to develop a multivalent polysaccharide vaccine to prevent most APEC infections. We previously reported the stable expression of plasmid pSS27 encoding the APEC O1 O-antigen gene cluster (10.8 kb) in attenuated Salmonella enterica serovar Typhimurium S740 provided excellent protection against APEC O1 challenge. In this study, the plasmid pSS28 harboring the APEC O2 O-antigen polysaccharide gene cluster (15.5 kb) was constructed. Biosynthesis of pSS28-encoded APEC O2 O-antigen in Salmonella vaccine strain S740 was validated by Western blot. The recombinant Salmonella vaccine strain S740 (pSS28) elicited homologous protection against virulent wild-type APEC O2 challenge in a chicken model. Furthermore, through equal-volume mixing the two monovalent vaccine strains S740 (pSS27) and S740 (pSS28), a bivalent vaccine candidate against both APEC O1 and O2 was developed. Immunization of chickens with the bivalent vaccine elicited production of serum IgG and mucosal sIgA antibodies against the LPS of both APEC O1 and O2. Moreover, antibodies induced by the bivalent vaccine promoted opsonization, provoked complement-mediated bactericidal activity, and elicited protection against lethal challenge with both virulent APEC O1 and O2 strains. These results demonstrate that the bivalent vaccine comprised of S740 (pSS27) and S740 (pSS28) is a promising vaccine candidate against APEC O1 and O2 infection.
禽致病性大肠杆菌（APEC）是导致禽气囊炎和大肠杆菌病的主要原因，给家禽业造成了巨大的经济损失。APEC 血清型 O1、O2 和 O78 与疾病的关系最为密切。脂多糖（LPS）O-抗原已被证明是诱导特异性保护免疫反应的有效抗原。因此，我们试图开发一种多价多糖疫苗来预防大多数 APEC 感染。我们之前报道了在减毒鼠伤寒沙门氏菌 S740 中稳定表达质粒 pSS27 编码的 APEC O1 O-抗原基因簇（10.8kb），该质粒提供了对 APEC O1 挑战的极好保护。在这项研究中，构建了携带 APEC O2 O-抗原多糖基因簇（15.5kb）的质粒 pSS28。Western blot 验证了 pSS28 编码的 APEC O2 O-抗原在沙门氏菌疫苗株 S740 中的生物合成。重组沙门氏菌疫苗株 S740（pSS28）在鸡模型中对强毒野生型 APEC O2 挑战产生同源保护。此外，通过将两种单价疫苗株 S740（pSS27）和 S740（pSS28）等体积混合，开发了一种针对 APEC O1 和 O2 的双价疫苗候选物。用双价疫苗免疫鸡可诱导针对 APEC O1 和 O2 LPS 的血清 IgG 和粘膜 sIgA 抗体产生。此外，双价疫苗诱导的抗体促进调理作用、引发补体介导的杀菌活性，并引发针对强毒 APEC O1 和 O2 菌株的致死性挑战的保护。这些结果表明，由 S740（pSS27）和 S740（pSS28）组成的双价疫苗是预防 APEC O1 和 O2 感染的一种有前途的疫苗候选物。
