Gahan Michelle E, Webster Diane E, Wijburg Odilia L C, Wesselingh Steven L, Strugnell Richard A
Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3052, Australia.
Vaccine. 2008 Nov 18;26(49):6212-20. doi: 10.1016/j.vaccine.2008.09.060. Epub 2008 Oct 11.
Recombinant Salmonella have been employed as vaccine vectors to deliver DNA and protein vaccines of viral, bacterial and parasitic origin. However, the effectiveness of Salmonella delivery may be hampered by prior immunological exposure to Salmonella. We investigated the effects of prior exposure to the Salmonella typhimurium aroAD strain BRD509 on its ability to deliver the non-toxic C fragment of tetanus toxin (TT). BALB/c mice were orally immunised with BRD509 containing the C fragment expression plasmid pTETtac4, C fragment DNA vaccine pAT153/Cfrag or BRD509 alone and, along with age matched un-vaccinated controls, were immunised again 6 months later with BRD509 (pTETtac4). Prior exposure to Salmonella was found to significantly reduce the ability of the bacteria to colonise the Peyer's patches and mesenteric lymph nodes, spread systemically to the liver and spleen and significantly impair antibody responses to Salmonella LPS and TT. Results show that prior exposure to Salmonella significantly compromises its efficacy as a vaccine vector and these negative effects do not diminish with time. In addition, findings suggest Salmonella vaccine vectors cannot be employed to deliver multiple doses of a vaccine antigen.
重组沙门氏菌已被用作疫苗载体，以递送病毒、细菌和寄生虫来源的DNA和蛋白质疫苗。然而，先前对沙门氏菌的免疫暴露可能会阻碍沙门氏菌递送疫苗的效果。我们研究了先前暴露于鼠伤寒沙门氏菌aroAD菌株BRD509对其递送破伤风毒素（TT）无毒C片段能力的影响。用含有C片段表达质粒pTETtac4的BRD509、C片段DNA疫苗pAT153/Cfrag或单独的BRD509对BALB/c小鼠进行口服免疫，并与年龄匹配的未接种对照一起，在6个月后再次用BRD509（pTETtac4）进行免疫。发现先前暴露于沙门氏菌会显著降低细菌定殖于派尔集合淋巴结和肠系膜淋巴结、全身扩散至肝脏和脾脏的能力，并显著损害对沙门氏菌LPS和TT的抗体反应。结果表明，先前暴露于沙门氏菌会显著损害其作为疫苗载体的功效，且这些负面影响不会随时间减弱。此外，研究结果表明沙门氏菌疫苗载体不能用于递送多剂量的疫苗抗原。
