Refined live attenuated Salmonella enterica serovar Typhimurium and Enteritidis vaccines mediate homologous and heterologous serogroup protection in mice.

Refined live attenuated Salmonella enterica serovar Typhimurium and Enteritidis vaccines mediate homologous and heterologous serogroup protection in mice.
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精制减毒活肠沙门氏菌血清型鼠伤寒和肠炎疫苗可介导小鼠的同源和异源血清群保护。

DOI:
10.1128/iai.00924-15
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发表时间:
2015
影响因子:
3.1
通讯作者:
Levine,MyronM
Levine,MyronM
中科院分区:
医学2区
文献类型:
--
作者:
Tennant,SharonM;Schmidlein,Patrick;Simon,Raphael;Pasetti,MarcelaF;Galen,JamesE;Levine,MyronM

文献摘要

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侵袭性非伤寒沙门氏菌(NTS)感染是撒哈拉以南非洲婴幼儿的主要健康问题;这些感染也发生在发达国家的婴儿和老年人中。我们对在撒哈拉以南非洲流行的主要基因型313型肠沙门氏菌血清型鼠伤寒杆菌进行了基因工程改造。我们评估了s的容量。鼠伤寒和肠炎沙门氏菌血清型ΔguaBAΔclpXlive口服疫苗保护小鼠免受同源血清型的高致死攻击剂量,并确定对撒哈拉以南非洲流行的其他B组和D组血清型的保护作用。疫苗。鼠伤寒CVD 1931和。Enteritidis CVD 1944免疫原性保护BALB/c小鼠抵抗10,000 50%致死剂量(LD50)的s。培养的口服补液盐。肠炎,respectively.S。鼠伤寒沙门氏菌CVD 1931能保护小鼠免受B组血清斯坦利维尔肠炎沙门氏菌的感染(疫苗有效率91%)。Enteritidis CVD 1944可保护小鼠免受D组血清都柏林型肠炎沙门氏菌的侵害(疫苗效力85%)。当小鼠在接种疫苗12周后感染时,观察到高存活率,表明疫苗引发了长期的保护性免疫。然而1931年的CVD并没有保护。Enteritidis R11, CVD 1944确实起到了保护作用。鼠伤寒杆菌D65(有效率81%)。这些发现提示一种二价的鼠伤寒沙门氏菌。肠炎疫苗将为撒哈拉以南非洲的大多数侵入性NTS感染提供广泛的保护。
Invasive nontyphoidal Salmonella (NTS) infections constitute a major health problem among infants and toddlers in sub-Saharan Africa; these infections also occur in infants and the elderly in developed countries. We genetically engineered a Salmonella enterica serovar Typhimurium strain of multilocus sequence type 313, the predominant genotype circulating in sub-Saharan Africa. We evaluated the capacities ofS. Typhimurium and Salmonella enterica serovar Enteritidis ΔguaBAΔclpXlive oral vaccines to protect mice against a highly lethal challenge dose of the homologous serovar and determined protection against other group B and D serovars circulating in sub-Saharan Africa. The vaccinesS. Typhimurium CVD 1931 andS. Enteritidis CVD 1944 were immunogenic and protected BALB/c mice against 10,000 50% lethal doses (LD50) ofS. Typhimurium orS. Enteritidis, respectively.S. Typhimurium CVD 1931 protected mice against the group B serovar Salmonella enterica serovar Stanleyville (91% vaccine efficacy), andS. Enteritidis CVD 1944 protected mice against the group D serovar Salmonella enterica serovar Dublin (85% vaccine efficacy). High rates of survival were observed when mice were infected 12 weeks postimmunization, indicating that the vaccines elicited long-lived protective immunity. Whereas CVD 1931 did not protect againstS. Enteritidis R11, CVD 1944 did mediate protection againstS. Typhimurium D65 (81% efficacy). These findings suggest that a bivalent (S. Typhimurium andS. Enteritidis) vaccine would provide broad protection against the majority of invasive NTS infections in sub-Saharan Africa.