Effective adjuvants for the induction of antigen-specific delayed type hypersensitivity
Effective adjuvants for the induction of antigen-specific delayed type hypersensitivity
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DOI：
10.1016/s0264-410x(96)00199-5
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发表时间：
1997-03-01
期刊：
影响因子：
5.5
通讯作者：
Ward, JR
中科院分区：
文献类型：
--
作者：
Baldridge, JR;Ward, JR
使用免疫原性差的亚单位抗原的疫苗依赖佐剂来驱动适当的T细胞反应。为了确定几种佐剂促进细胞免疫(CMI)的能力，我们评估了接种热灭活单核细胞增生性李斯特菌(HKLM)疫苗的小鼠的迟发型超敏反应(DTH)。这些疫苗是以水包油乳剂的形式配制的，其中包含以下一种或多种细菌来源的免疫刺激剂。MPL(R)免疫刺激剂，单磷酰脂A制备合成海藻糖二核苷酸(TDCM)和草分枝杆菌细胞壁骨架(CWS)。不含佐剂的HKLM水包油乳剂对小鼠迟发型超敏反应无明显影响。在配方中加入TDCM或MPL(R)+TDCM和/或CWS，使HKLM疫苗能够刺激以迟发型过敏反应为特征的CMI。抗原攻击后，足垫厚度增加15-20%，与完全弗氏佐剂所致的迟发型超敏反应相当。由MPL/TDCM和MPL/TDCM/CWS组成的佐剂诱导的反应与活单核细胞增多性李斯特菌免疫小鼠的反应相当，并保持在这些水平至少2个月。此外，体内CD4+T细胞的耗尽，而不是CD8+T细胞的耗尽，抑制了迟发型变态反应的诱导和表达，表明这种反应是由CD4+T细胞介导的。(C)1997年爱思唯尔科学有限公司。
Vaccines utilizing poorly immunogenic subunit antigens are dependent upon adjuvants to drive the appropriate T cell responses. In an effort to determine the ability of several adjuvants to promote cell-mediated immunity (CMI), we assessed delayed-type hypersensitivity (DTH) in mice inoculated with heat-killed Listeria monocytogenes (HKLM) vaccines. The vaccines were formulated as oil-in-water emulsions containing one or more of the following bacterial-derived immunostimulators. MPL(R) immunostimulant, a monophosphoryl lipid A preparation synthetic trehalose dicorynomycolate (TDCM) and Mycobacterium phlei cell wall skeleton (CWS). Oil-in-water emulsions containing HKLM without adjuvants did not induce DTH responsiveness in mice. The incorporation of TDCM, or MPL(R) plus TDCM and/or CWS to the formulation enabled the HKLM vaccine to stimulate CMI characterized by DTH responsiveness. Following antigen challenge the resulting increases in footpad thickness ranged from 15-20% and were comparable to the DTH driven by complete Freund's adjuvant. Adjuvants composed of MPL/TDCM and MPL/TDCM/CWS induced responses equivalent to those measured in mice immunized with viable L. monocytogenes, and the responses remained at these levels for at least 2 months. Furthermore, in vivo depletion of CD4+ T cells, but not CD8+ T cells, abrogated the induction and expression of DTH, indicating that the response is mediated by CD4+ T cells. (C) 1997 Elsevier Science Ltd.