Regulated delayed attenuation improves vaccine efficacy in preventing infection from avian pathogenic Escherichia coli O78 and Salmonella typhimurium
Regulated delayed attenuation improves vaccine efficacy in preventing infection from avian pathogenic Escherichia coli O78 and Salmonella typhimurium
复制标题
调节延迟减毒可提高疫苗预防禽致病性大肠杆菌 O78 和鼠伤寒沙门氏菌感染的功效
DOI：
10.1016/j.vetmic.2021.109012
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发表时间：
2021-02-18
影响因子：
3.3
通讯作者：
Song, Houhui
中科院分区：
文献类型：
--
作者：
Han, Yue;Luo, Ping;Song, Houhui
禽致病性大肠杆菌（APEC）O-78和鼠伤寒沙门氏菌（S。鼠伤寒沙门氏菌（Typhimurium）是导致家禽业重大经济损失的两种主要细菌病原体。O抗原是这两种细菌在感染过程中诱导宿主保护性免疫反应的重要免疫原。目的研制抗O-78和S.本研究以鼠伤寒沙门氏菌（Salmonella St 01，Delta asd Delta rfbp Delta crp）为载体，构建了携带APCO-78 O抗原多糖（OPS）的减毒沙门氏菌（Salmonella ST 01，Delta asd Delta rfbp Delta crp），并在asd（+）平衡致死系统中稳定表达OPS。口服免疫后，重组减毒沙门氏菌疫苗（RASV）菌株ST 01（pSS 26-O-78）对APEC O-78攻击的保护不足。因此，通过用araC PBAD盒调节环AMP受体蛋白（crp）以更好地将异源O-抗原呈递给宿主免疫系统，进一步构建了调节延迟减毒菌株ST 02（Delta asd Delta rfbp Delta pcrp：：TTaraC P-BAD crp）。创新的重组菌株ST 02（pSS 26-O-78）刺激针对APEC O-78和S.鼠伤寒沙门氏菌OPS，IgG和伊加的血清滴度均超过1：800，从而提供补体介导的杀菌活性和对APEC O-78和S.鼠伤寒感染。总的来说，这项研究证明了一种生物结合的多糖疫苗候选者，可以增强对APEC O-78和S。鼠伤寒
Avian pathogenic Escherichia coli (APEC) O-78 and Salmonella typhimurium (S. Typhimurium) are two leading bacterial pathogens that cause significant economic loss in the poultry industry. O-antigen is an important immunogen of these two bacteria to induce host protective immune responses during infection. To develop a bivalent vaccine against APEC O-78 and S. Typhimurium, the attenuated Salmonella ST01 (Delta asd Delta rfbp Delta crp) was genetically constructed to deliver APEC O-78 O-antigen polysaccharide (OPS), which stably expresses OPS with asd(+) balanced-lethal system in vitro and in vivo. After oral immunization, the recombinant attenuated Salmonella vaccine (RASV) strain ST01 (pSS26-O-78) provided insufficient protection against the APEC O-78 challenge. Therefore, the regulated delayed attenuation strain ST02 (Delta asd Delta rfbp Delta pcrp::TTaraC P-BAD crp) was further constructed by regulating cyclic AMP receptor protein (crp) with araC PBAD cassette to better present the heterologous O-antigen to the host immune system. The innovative recombinant strain ST02 (pSS26-O-78) stimulated robust antibody responses against APEC O-78 and S. Typhimurium OPS, with serum titers over 1:800 for both IgG and IgA, thereby providing the complement-mediated bactericidal activity and stronger protection against APEC O-78 and S. Typhimurium infection. Collectively, this study demonstrates a biologically-conjugated polysaccharide vaccine candidate that can enhance homologous protection against APEC O-78 and S. Typhimurium.