Genetically Detoxified Mutants of Heat-Labile Toxin from Escherichia coli Are Able To Act as Oral Adjuvants
Genetically Detoxified Mutants of Heat-Labile Toxin from Escherichia coli Are Able To Act as Oral Adjuvants
复制标题
大肠杆菌不耐热毒素的基因脱毒突变体能够充当口服佐剂
作者：
G. Douce;V. Giannelli;M. Pizza;D. Lewis;P. Everest;R. Rappuoli;G. Dougan
摘要大肠杆菌不耐热毒素(LT)的解毒突变体可作为鼻腔给药联合抗原的黏膜佐剂。在这里，我们比较了一组LT的解毒衍生物的佐剂活性，使用鼻腔(I.N.)和口头(P.O.)管理途径。作为佐剂的突变体对酶的敏感性和毒性各不相同。以锁孔帽状血蓝蛋白(KLH)为旁观者抗原，观察其对I.N.免疫接种率始终高于等量的P.O.递送蛋白。突变体LT-G192在体外毒性降低10倍，表现出野生型佐剂活性。和P.O.，在血清中诱导产生与野生型LT相似的KLH特异性抗体，在局部粘膜分泌物中诱导免疫球蛋白A滴度。与以前的数据一致，无毒的全毒素LT-K63在血清和粘膜分泌物中诱导的中间免疫反应低于野生型LT，但至少比给予LT-B抗原时高10倍。虽然P.O.可诱导出显著水平的局部和全身抗KLH抗体。LT-K63免疫后，细胞对KLH的增殖反应较差或检测不到。相反，LT和LT-G192在P.O后诱导了显著的T细胞对KLH的反应。免疫接种。这些增殖细胞同时分泌γ-干扰素和白介素5，提示P.O.LT和纯化蛋白的联合免疫是一种混合的Th1/Th2反应。
ABSTRACT Detoxified mutants of the Escherichia coli heat-labile toxin (LT) act as mucosal adjuvants to intranasally presented coadministered antigens. Here, we compare the adjuvant activity of a panel of detoxified derivatives of LT, using both intranasal (i.n.) and oral (p.o.) routes of administration. The mutants used as adjuvants varied in sensitivity to proteases and toxicity. With keyhole limpet hemocyanin (KLH) as the bystander antigen, the immune responses to i.n. immunizations were consistently higher than the equivalent p.o.-delivered proteins. LT-G192, a mutant which demonstrates a 10-fold reduction in toxicity in vitro, demonstrated wild-type adjuvant activity both i.n. and p.o., inducing similar titers of KLH specific antibody in the sera and immunoglobulin A in local mucosal secretions as wild-type LT. In line with previous data, the nontoxic holotoxoid LT-K63 induced intermediate immune responses in both the serum and mucosal secretions which were lower than those achieved with wild-type LT but at least 10-fold higher than those measured when the antigen was administered with LT-B. Although significant levels of local and systemic anti-KLH antibodies were induced following p.o. immunization with LT-K63, cellular proliferative responses to KLH was poor or undetectable. In contrast, LT and LT-G192 induced significant T-cell responses to KLH following p.o. immunization. These proliferating cells secreted both gamma interferon and interleukin-5, suggesting that the type of immune response induced following p.o. coimmunization with LT and purified protein is a mixed Th1/Th2 response.
通过口服免疫诱导肺炎球菌多糖特异性粘膜免疫反应。
影响因子：
5.5
作者：
VanCott,JL;Kobayashi,T;Yamamoto,M;Pillai,S;McGhee,JR;Kiyono,H
通讯作者：
Kiyono,H
DOI：
10.1073/pnas.94.10.5267
发表时间：
1997-05-13
影响因子：
11.1
作者：
Yamamoto, S;Kiyono, H;McGhee, JR
通讯作者：
McGhee, JR