College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, Jiangsu, China; Jiangsu Co-innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611-0880, USA.
Vaccine. 2023 Sep 22;41(41):5951-5956. doi: 10.1016/j.vaccine.2023.08.078. Epub 2023 Sep 4.
Interference with the normal synthesis of LPS was shown to enhance immune responses to conserved outer membrane proteins. In the present study, we have constructed three vaccine candidates by deleting four genes (rfaL, rfbB, rffG and wzy) associated with LPS synthesis in the wild-type strain UK-1. Virulence assessment showed that after oral immunization of BALB/c mice, all mutant strains were attenuated and had significantly reduced ability to colonize host tissues compared to the wild-type strain. In addition, all three vaccine candidates induced elevated humoral, mucosal and cellular immune responses against S. Typhimurium and S. Choleraesuis OMPs compared to the PBS-treated group. Finally, immunization of mice with the rSC0136 vaccine candidate strain provided 100 % and 40 % protection against S. Typhimurium and S. Choleraesuis challenge, respectively. These results suggest that the deletion of LPS synthesis-related genes may be an effective strategy against homologous serotypes, but provides only partial protection against heterologous serotypes.
干扰 LPS 的正常合成被证明可以增强对保守的外膜蛋白的免疫反应。在本研究中，我们通过删除与野生型 UK-1 菌株 LPS 合成相关的四个基因（rfaL、rfbB、rffG 和 wzy）构建了三种疫苗候选物。毒力评估表明，经口服免疫接种 BALB/c 小鼠后，与野生型菌株相比，所有突变株的毒力均减弱，定植宿主组织的能力显著降低。此外，与 PBS 处理组相比，所有三种疫苗候选物均诱导针对鼠伤寒沙门氏菌和猪霍乱沙门氏菌 OMP 的体液、黏膜和细胞免疫应答升高。最后，用 rSC0136 疫苗候选菌株免疫小鼠可分别提供针对鼠伤寒沙门氏菌和猪霍乱沙门氏菌攻击的 100%和 40%的保护。这些结果表明，删除 LPS 合成相关基因可能是针对同源血清型的有效策略，但仅提供针对异源血清型的部分保护。
