PDF(Pubmed)
Abstract：
Nontyphoidal Salmonella enterica (NTS) is a leading cause of foodborne illness worldwide, including in the United States, where infants show the highest incidence amongst all age groups. S. enterica serovar Typhimurium is one of the most frequently isolated serovars from NTS infections. We have developed several candidate live-attenuated S. Typhimurium vaccines to prevent NTS infection. The goal of the current study was to assess three live S. Typhimurium vaccine strains (CVD 1921, CVD 1921 ∆htrA and CVD 1926, which have two, three and four gene deletions, respectively) with various levels of reactogenicity and immunogenicity in infant BALB/c mice to predict how they would perform following peroral immunization of infants. We first tested intranasal immunization of 14-day-old mice with three doses delivered at 1-week intervals and evaluated antibody responses and protection against lethal infection with wild-type S. Typhimurium. The vaccines were administered to 14-day-old mice via the peroral route at 1- or 2-week intervals and to 28-day-old mice at 2-week intervals. The three vaccine strains were immunogenic following intranasal immunization of infant mice with vaccine efficacies of 80% (CVD 1921), 63% (CVD 1921 ∆htrA) and 31% (CVD 1926). In contrast, peroral immunization of 14-day-old mice yielded much poorer protection against lethal infection and only immunization of 28-day-old mice at 2-week intervals showed similar protective capacity as intranasal administration (CVD 1921: 83%, CVD 1921 ∆htrA: 43% and CVD 1926: 58%). CVD 1921 was consistently more protective than both CVD 1921 ∆htrA and CVD 1926, regardless of the route of vaccination, immunization schedule and age of mice. Anti-LPS serum IgG responses were similar between the three strains and did not correlate with protection. Due to previously observed reactogenicity of CVD 1921, CVD 1921 ∆htrA and CVD 1926 are our preferred vaccines, but these data show that further improvements would need to be made to achieve suitable protection in young infants when using peroral immunization.
摘要：
非伤寒沙门氏菌（NTS）是全球食源性疾病的主要原因，包括在美国,在所有年龄组中，婴儿的发病率最高。肠球菌血清变型鼠伤寒沙门氏菌是NTS感染中最常见的分离血清变型之一。我们已经开发了几种候选的减毒活鼠伤寒沙门氏菌疫苗来预防NTS感染。本研究的目标是评估三种活的鼠伤寒沙门氏菌疫苗株（CVD1921，CVD1921ΔhtrA和CVD1926，它们有两种，三个和四个基因缺失，分别）在婴儿BALB/c小鼠中具有不同水平的反应原性和免疫原性，以预测婴儿经口免疫后的表现。我们首先测试了以1周间隔递送的三个剂量的14日龄小鼠的鼻内免疫,并评估了抗体应答和针对野生型鼠伤寒沙门氏菌的致死性感染的保护。将疫苗以1或2周的间隔经口途径施用于14日龄小鼠,并以2周的间隔施用于28日龄小鼠。三种疫苗株在鼻内免疫婴儿小鼠后具有免疫原性，疫苗效力为80％（CVD1921），63%（CVD1921ΔHTRA）和31%（CVD1926）。相比之下,14日龄小鼠的经口免疫对致死性感染的保护作用要差得多，只有以2周的间隔免疫28日龄小鼠显示出与鼻内给药相似的保护能力（CVD1921：83％，CVD1921ΔHTRA：43%，CVD1926：58%）。无论疫苗接种途径如何，CVD1921始终比CVD1921和CVD1926更具保护性，免疫计划和小鼠的年龄。三种菌株之间的抗LPS血清IgG反应相似，与保护无关。由于先前观察到的CVD1921的反应原性，CVD1921ΔhtrA和CVD1926是我们的首选疫苗，但是这些数据表明，在使用经口免疫时，需要进一步改进以实现对年轻婴儿的适当保护。
