Construction of Recombinant Attenuated Salmonella enterica Serovar Typhimurium Vaccine Vector Strains for Safety in Newborn and Infant Mice
Construction of Recombinant Attenuated Salmonella enterica Serovar Typhimurium Vaccine Vector Strains for Safety in Newborn and Infant Mice
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DOI：
10.1128/cvi.00412-09
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发表时间：
2010-03-01
影响因子：
--
通讯作者：
Curtiss, Roy, III
中科院分区：
文献类型：
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作者：
Gunn, Bronwyn M.;Wanda, Soo-Young;Curtiss, Roy, III
重组细菌疫苗必须安全、有效且耐受性良好，特别是在给新生儿和婴儿接种以预防幼儿疾病时。许多减毒手段已显示使疫苗株对宿主防御敏感或不能有效地定殖淋巴组织，从而降低其免疫原性。我们已经构建了重组减毒沙门氏菌疫苗株，其显示高水平的减毒，同时保留诱导高水平免疫原性的能力，并且当给予24小时大的婴儿小鼠时，在高剂量下耐受良好。这些菌株含有三种调节延迟减毒的方法，以及一系列额外的突变，这些突变有助于提高安全性，调节抗原表达，并减少通常与沙门氏菌感染相关的疾病症状。当以高达3.5 × 10（8）CFU的剂量经口给予24 h龄的幼鼠时，疫苗株耐受性良好。
Recombinant bacterial vaccines must be safe, efficacious, and well tolerated, especially when administered to newborns and infants to prevent diseases of early childhood. Many means of attenuation have been shown to render vaccine strains susceptible to host defenses or unable to colonize lymphoid tissue effectively, thus decreasing their immunogenicity. We have constructed recombinant attenuated Salmonella vaccine strains that display high levels of attenuation while retaining the ability to induce high levels of immunogenicity and are well tolerated in high doses when administered to infant mice as young as 24 h old. The strains contain three means of regulated delayed attenuation, as well as a constellation of additional mutations that aid in enhancing safety, regulate antigen expression, and reduce disease symptoms commonly associated with Salmonella infection. The vaccine strains are well tolerated when orally administered to infant mice 24 h old at doses as high as 3.5 x 10(8) CFU.