New technologies in using recombinant attenuated Salmonella vaccine vectors.

New technologies in using recombinant attenuated Salmonella vaccine vectors.
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DOI:
10.1615/critrevimmunol.v30.i3.30
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发表时间:
2010
影响因子:
1.3
通讯作者:
Wang S
Wang S
中科院分区:
医学4区
文献类型:
--
作者:
Curtiss R 3rd;Xin W;Li Y;Kong W;Wanda SY;Gunn B;Wang S

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已经构建了重组减毒沙门氏菌疫苗(RASV)以递送来自其他病原体的抗原,从而在接种疫苗的宿主中诱导对这些病原体的免疫。减毒手段应确保疫苗在接种后存活以定殖淋巴组织而不引起疾病症状。这就需要重组基因编码的保护性抗原的减毒和合成不降低口服给药的疫苗在胃肠道中遇到的应激中存活的能力。我们已经通过使用具有减毒的调节延迟表达和重组抗原的调节延迟合成的RASV消除了这些问题。这些变化导致RASV有效地定殖效应淋巴组织以充当合成保护性抗原的“工厂”,所述保护性抗原诱导比使用先前构建的RASV时所实现的更高的保护性免疫应答。我们设计了一种生物遏制系统,具有调节的延迟裂解,以排除RASV在体内的持续存在和排泄后的存活。添加属性以减少口服活RASV时有时发生的轻度腹泻,并确保新生儿完全安全。这些技术已被用于开发一种新的、低成本的、RASV合成的、多重保护性肺炎链球菌抗原,该抗原对新生儿/婴儿是安全的,并将诱导对多种肺炎链球菌的保护性免疫。肺炎血清型。
Recombinant attenuated Salmonella vaccines (RASVs) have been constructed to deliver antigens from other pathogens to induce immunity to those pathogens in vaccinated hosts. The attenuation means should ensure that the vaccine survives following vaccination to colonize lymphoid tissues without causing disease symptoms. This necessitates that attenuation and synthesis of recombinant gene encoded protective antigens do not diminish the ability of orally administered vaccines to survive stresses encountered in the gastrointestinal tract. We have eliminated these problems by using RASVs with regulated delayed expression of attenuation and regulated delayed synthesis of recombinant antigens. These changes result in RASVs that colonize effector lymphoid tissues efficiently to serve as “factories” to synthesize protective antigens that induce higher protective immune responses than achieved when using previously constructed RASVs. We have devised a biological containment system with regulated delayed lysis to preclude RASV persistence in vivo and survival if excreted. Attributes were added to reduce the mild diarrhea sometimes experienced with oral live RASVs and to ensure complete safety in newborns. These collective technologies have been used to develop a novel, low-cost, RASV-synthesizing, multiple-protective Streptococcus pneumoniae antigens that will be safe for newborns/infants and will induce protective immunity to diverse S. pneumoniae serotypes after oral immunization.
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