The potential Salmonella aroA- vaccine strain is safe and effective in young BALB/c mice

The potential Salmonella aroA- vaccine strain is safe and effective in young BALB/c mice
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DOI:
10.1159/000097128
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发表时间:
2007-01-01
期刊:
影响因子:
2.5
通讯作者:
Contag, Christopher H.
Contag, Christopher H.
中科院分区:
医学2区
文献类型:
--
作者:
Burns-Guydish, Stacy M.;Zhao, Hui;Contag, Christopher H.

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背景资料:由于新生儿对病原体(包括突变病原体)的易感性增加,在人群中使用活疫苗策略可能对年轻人构成潜在风险。目的:本研究的具体目的是评估预期的肠道沙门氏菌鼠伤寒血清型疫苗菌株对新生儿造成的风险,并通过评估适应性免疫应答确定菌株是否是有效的疫苗。方法:采用免疫敏感性试验方法,观察乳鼠对疫苗株S.鼠伤寒aroA(-)和Δ phoP突变株通过lux操纵子的染色体插入来标记,这用作使用非侵入性成像方法的容易追踪的感染标记。给1、2、4和6周龄的BALB/c小鼠喂食生物发光aroA(-)或Delta phoP菌株,并通过体内生物发光成像监测感染过程。此外,在接种后收集血液样品以评估小鼠对S.鼠伤寒杆菌LPS。结果如下:与10(9)个集落形成单位剂量下对Delta phoP菌株的敏感性相反,幼龄BALB/c小鼠对aroA菌株不敏感。通过口服喂食aroA(-)和Delta phoP菌株在年轻小鼠中的递送也产生了强有力的IgG抗LPS应答。结论:在这里,我们报告了年轻的2周龄小鼠口服生物发光aroA(-)S。鼠伤寒沙门氏菌菌株对感染不敏感,并引起保护性免疫应答。版权所有(c)2007 S. Karger AG,巴塞尔。
Background: Due to the increased susceptibility of neonates to pathogens including those with mutations, the use of live vaccine strategies in the human population may present a potential risk to the young. Objectives: The specific aim of this study was to assess the risk that prospective Salmonella enterica serovar Typhimurium vaccine strains pose for the neonate and determine whether the strains are an effective vaccine by assessing the adaptive immune response. Methods: To evaluate the susceptibility of young mice to potential vaccine strains, S. typhimurium aroA(-) and Delta phoP mutant strains were labeled by chromosomal insertion of the lux operon-this serves as a readily traceable marker of infection using noninvasive imaging methods. BALB/c mice ages 1, 2, 4, and 6 weeks of age were fed the bioluminescent aroA(-) or Delta phoP strains and the course of infection was monitored by in vivo bioluminescence imaging. In addition, blood samples were collected post-inoculation to assess the IgG response of mice to S. typhimurium LPS. Results: Young BALB/c mice were not susceptible to the aroA strain in contrast to their susceptibility to the Delta phoP strain at a dose of 10(9) colony forming units. Delivery by oral feeding of the aroA(-) and Delta phoP strains in young mice also produced a robust IgG anti-LPS response. Conclusion: Here, we report that young 2-week-old mice orally fed the bioluminescent aroA(-) S. typhimurium strain were not susceptible to infection and elicited a protective immune response. Copyright (c) 2007 S. Karger AG, Basel.