The Immunogenicity and Properties of a Whole-Cell ETEC Vaccine Inactivated with Psoralen and UVA Light in Comparison to Formalin.
The Immunogenicity and Properties of a Whole-Cell ETEC Vaccine Inactivated with Psoralen and UVA Light in Comparison to Formalin.
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DOI：
10.3390/microorganisms11082040
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发表时间：
2023-08-09
期刊：
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
--
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灭活的全细胞疫苗向免疫系统提供完整的抗原库。福尔马林处理是微生物灭活的标准方法，可以修饰或破坏蛋白质抗原表位。我们测试了这样一种假设，即用靶向核酸的peptide和UVA光（PUVA）进行光化学灭活，将提高产肠球菌E.大肠杆菌（ETEC）疫苗相对于福尔马林灭活的对应物。将ETEC H10407暴露于PUVA（使用头孢菌素药物4′-氨甲基三恶沙林盐酸盐（AMT）），产生了保留代谢活性的无复制能力细菌。CFA/I介导的甘露糖抗性血凝（MRHA）对于PUVA灭活的和活的ETEC是等效的，但对于福尔马林-ETEC是严重降低的，表明PUVA保留了菌毛蛋白功能的完整性。在小鼠±双突变不耐热肠毒素（dmLT）佐剂中比较PUVA-ETEC和福尔马林-ETEC的免疫原性。肌内初免/加强免疫后2周，两种疫苗的血清抗ETEC IgG滴度相似，并且通过dmLT增加。然而，接种PUVA-ETEC后，针对几种保守ETEC蛋白的IgG应答更高。此外，在不存在dmLT的情况下，PUVA-ETEC产生了对热不稳定毒素（LT）具有特异性的IgG，这不是福尔马林-ETEC的特性。这些数据与PUVA以天然样形式保存ETEC蛋白抗原一致，并证明了使用鼠攻毒模型进一步检测PUVA作为ETEC疫苗平台的合理性。
Inactivated whole-cell vaccines present a full repertoire of antigens to the immune system. Formalin treatment, a standard method for microbial inactivation, can modify or destroy protein antigenic epitopes. We tested the hypothesis that photochemical inactivation with psoralen and UVA light (PUVA), which targets nucleic acid, would improve the immunogenicity of an Enterotoxigenic E. coli (ETEC) vaccine relative to a formalin-inactivated counterpart. Exposure of ETEC H10407 to PUVA using the psoralen drug 4′-Aminomethyltrioxsalen hydrochloride (AMT) yielded replication-incompetent bacteria that retained their metabolic activity. CFA/I-mediated mannose-resistant hemagglutination (MRHA) was equivalent for PUVA-inactivated and live ETEC, but was severely reduced for formalin–ETEC, indicating that PUVA preserved fimbrial protein functional integrity. The immunogenicity of PUVA–ETEC and formalin–ETEC was compared in mice ± double mutant heat-labile enterotoxin (dmLT) adjuvant. Two weeks after an intramuscular prime/boost, serum anti-ETEC IgG titers were similar for the two vaccines and were increased by dmLT. However, the IgG responses raised against several conserved ETEC proteins were greater after vaccination with PUVA–ETEC. In addition, PUVA–ETEC generated IgG specific for heat-labile toxin (LT) in the absence of dmLT, which was not a property of formalin–ETEC. These data are consistent with PUVA preserving ETEC protein antigens in their native-like form and justify the further testing of PUVA as a vaccine platform for ETEC using murine challenge models.
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影响因子：
82.9
作者：
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通讯作者：
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3.1
作者：
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