LT-IIb(T13I), a Non-Toxic Type II Heat-Labile Enterotoxin, Augments the Capacity of a Ricin Toxin Subunit Vaccine to Evoke Neutralizing Antibodies and Protective Immunity
LT-IIb(T13I), a Non-Toxic Type II Heat-Labile Enterotoxin, Augments the Capacity of a Ricin Toxin Subunit Vaccine to Evoke Neutralizing Antibodies and Protective Immunity
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DOI：
10.1371/journal.pone.0069678
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发表时间：
2013-08-02
期刊：
影响因子：
3.7
通讯作者：
Connell, Terry D.
中科院分区：
文献类型：
--
作者：
Greene, Christopher J.;Chadwick, Chrystal M.;Connell, Terry D.
目前，缺乏可与蛋白质亚单位疫苗一起使用以增强对生物威胁的保护的佐剂。LT-IIb（T13 I）是LT-IIb的工程无毒衍生物，LT-IIb是由大肠杆菌表达的热不稳定肠毒素的II型亚家族的成员，具有有效的粘膜佐剂特性。在这项研究中，我们评估了LT-IIb（T13 I）在通过皮内（i.d.）和鼻内（i.n.）航线我们报告了通过i.d.与单独的RiVax相比，通过RiVax途径增强了RiVax特异性血清IgG抗体（Ab）的水平，并提高了蓖麻毒素中和抗体与非中和抗体的比率。LT-IIb（T13 I）也增强了对致命蓖麻毒素攻击的保护。虽然由LT-IIb（T13 I）引起的局部炎症反应与由铝盐（Imject（R））引起的那些相当，但LT-IIb（T13 I）在增加RiVax特异性血清IgG的产生方面比铝盐更有效。最后，i.n.与LT-IIb（T13 I）一起施用RiVax也增加了RiVax特异性血清和粘膜Ab的水平，并增强了对蓖麻毒素攻击的保护。总的来说，这些数据突出了LT-IIb（T13 I）作为有效的下一代i.d.的潜力，或者可能是I.N.增强生物防御亚单位疫苗免疫原性的佐剂。
Currently, there is a shortage of adjuvants that can be employed with protein subunit vaccines to enhance protection against biological threats. LT-IIb(T13I) is an engineered nontoxic derivative of LT-IIb, a member of the type II subfamily of heat labile enterotoxins expressed by Escherichia coli, that possesses potent mucosal adjuvant properties. In this study we evaluated the capacity of LT-IIb(T13I) to augment the potency of RiVax, a recombinant ricin toxin A subunit vaccine, when co-administered to mice via the intradermal (i.d.) and intranasal (i.n.) routes. We report that co-administration of RiVax with LT-IIb(T13I) by the i.d. route enhanced the levels of RiVax-specific serum IgG antibodies (Ab) and elevated the ratio of ricin-neutralizing to non-neutralizing Ab, as compared to RiVax alone. Protection against a lethal ricin challenge was also augmented by LT-IIb(T13I). While local inflammatory responses elicited by LT-IIb(T13I) were comparable to those elicited by aluminum salts (Imject (R)), LT-IIb(T13I) was more effective than aluminum salts at augmenting production of RiVax-specific serum IgG. Finally, i.n. administration of RiVax with LT-IIb(T13I) also increased levels of RiVax-specific serum and mucosal Ab and enhanced protection against ricin challenge. Collectively, these data highlight the potential of LT-IIb(T13I) as an effective next-generation i.d., or possibly i.n. adjuvant for enhancing the immunogenicity of subunit vaccines for biodefense.