Monophosphoryl lipid A enhances specific CTL induction by a soluble protein antigen entrapped in liposomes.
Monophosphoryl lipid A enhances specific CTL induction by a soluble protein antigen entrapped in liposomes.
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单磷酰脂质 A 通过包裹在脂质体中的可溶性蛋白抗原增强特异性 CTL 诱导。
DOI：
10.1016/0264-410x(93)90076-a
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发表时间：
1993
期刊：
影响因子：
5.5
通讯作者：
Huang,L
中科院分区：
文献类型：
--
作者：
Zhou,F;Huang,L
将外源性可溶性抗原负载于包括脾细胞和脂质体的膜载体中可以在小鼠中诱导CD8+细胞毒性T淋巴细胞（CTL）应答。然而，简单组成的普通脂质体不如细胞载体如脾细胞有效。在本研究中，它表明，掺入单磷酰脂质A（MPL），半合成的细菌佐剂，脂质体增强的能力，脂质体卵清蛋白（OVA）引发特异性CTL反应。使用MPL制剂，可检测的CTL诱导所需的最小抗原剂量减少约五倍，这接近脾细胞中所需的最小OVA剂量。此外，含有MPL的脂质体可以通过静脉内、肌肉内或皮下免疫方案诱导相当水平的CTL活性，而不含MPL的脂质体只能通过静脉内注射途径引起这种应答。皮下注射含有MPL的脂质体和含有抗原的脂质体的混合物也引起特异性CTL活性。然而，在两个远距离位点同时皮下施用脂质体MPL和脂质体OVA没有引发小鼠的CTL应答。这些结果表明，MPL，虽然不一定掺入相同的脂质体，必须在接近抗原发挥其佐剂活性。基于该模型抗原研究的结果，建议最佳CTL诱导疫苗除了I类途径递送载体如脂质体之外还应包括免疫调节佐剂。
Exogenous soluble antigen loaded in membranous vehicles including splenocytes and liposomes can induce a CD8+ cytotoxic T-lymphocyte (CTL) response in mice. Plain liposomes of simple composition, however, are not as effective as cellular vehicles such as splenocytes. In the present study it is shown that incorporation of monophosphoryl lipid A (MPL), a semisynthetic bacterial adjuvant, into liposomes enhanced the ability of liposomal ovalbumin (OVA) to prime for a specific CTL response. With the MPL formulation, the minimal antigen dose required for a detectable CTL induction was reduced about fivefold, and this approximated the required minimal dose of OVA loaded in the splenocytes. Moreover, liposomes containing MPL could induce a considerable level of CTL activity by either an intravenous, intramuscular or subcutaneous immunization protocol, whereas liposomes without MPL could only elicit such a response by an intravenous injection route. Subcutaneous injection of a mixture of liposomes containing MPL and liposomes containing antigen also elicited specific CTL activity. However, simultaneous subcutaneous administration of liposomal MPL and liposomal OVA at two distant sites did not prime the mice for a CTL response. These results indicate that MPL, although not necessarily incorporated in the same liposomes, must be in close proximity to the antigen to exert its adjuvant activity. Based on the results of this model antigen study, it is suggested that an optimal CTL inductive vaccine should include immunomodulatory adjuvant in addition to a class I pathway delivery vehicle such as liposomes.