Intradermal administration of the Type II heat-labile enterotoxins LT-IIb and LT-IIc of enterotoxigenic Escherichia coli enhances humoral and CD8+ T cell immunity to a co-administered antigen.
Intradermal administration of the Type II heat-labile enterotoxins LT-IIb and LT-IIc of enterotoxigenic Escherichia coli enhances humoral and CD8+ T cell immunity to a co-administered antigen.
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DOI：
10.1371/journal.pone.0113978
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Connell TD
中科院分区：
文献类型：
--
作者：
Hu JC;Mathias-Santos C;Greene CJ;King-Lyons ND;Rodrigues JF;Hajishengallis G;Ferreira LC;Connell TD
接种疫苗对防治传染病极为有效。然而，许多保守的抗原（Ag）靶点的免疫原性很差。蛋白质亚单位疫苗通常只引起体液免疫反应，不能对严重的细胞内病原体提供保护。这些阻碍疫苗开发的障碍通常可以通过使用适当的佐剂来克服。大肠杆菌产肠毒素菌株产生的热不稳定肠毒素（HLT）通过粘膜或全身途径给药时是有效的佐剂。然而，当采用皮内（ID）途径给药时，II型HLT的疗效尚未明确。采用小鼠ID免疫模型，比较了两种II型HLT LT-IIb和LT-IIc与典型I型HLT LT-I的佐剂特性。虽然所有三种HLT佐剂都将ag特异性体液反应增强到相似的水平，但与LT-I相比，LT-IIb和LT-IIc诱导了更强烈的ag特异性CD8+ T细胞反应，并在攻击模型中提供了更快的单核细胞增生李斯特菌清除。此外，LT-IIb和LT-IIc诱导了ag特异性CD8+ T细胞反应谱的明显差异。虽然LT-IIc刺激了强大而快速的原代CD8+ T细胞反应，但LT-IIb表现出较慢的CD8+ T细胞扩张和收缩动力学，并形成较高百分比的效应记忆细胞。与LT-I和LT-IIc相比，LT-IIb在免疫后具有更好的长期保护作用。此外，LT-IIb和LT-IIc增加了引流淋巴结（DLN）中树突状细胞（DC）的总数和DC上共刺激分子CD80、CD86和CD40的表达。与LT-I相比，LT-IIb和LT-IIc在ID注射部位诱导的水肿、细胞浸润和一般炎症较少。因此，LT-IIb和LT-IIc是有吸引力的综合ID佐剂，具有独特的特性，可以增强对共同给药蛋白Ag的体液和细胞免疫。
Vaccinations are extremely effective at combating infectious diseases. Many conserved antigen (Ag) targets, however, are poorly immunogenic. Protein subunit vaccines frequently elicit only humoral immune responses and fail to confer protection against serious intracellular pathogens. These barriers to vaccine development are often overcome by the use of appropriate adjuvants. Heat-labile enterotoxins (HLT) produced by enterotoxigenic strains of Escherichia coli are potent adjuvants when administered by mucosal or systemic routes. The efficacy of the type II HLT, however, has not been well-defined when administered by the intradermal (ID) route. Using a murine ID immunization model, the adjuvant properties of LT-IIb and LT-IIc, two type II HLTs, were compared with those of LT-I, a prototypical type I HLT. While all three HLT adjuvants enhanced Ag-specific humoral responses to similar levels, LT-IIb and LT-IIc, in contrast to LT-I, induced a more vigorous Ag-specific CD8+ T cell response and proffered faster clearance of Listeria monocytogenes in a challenge model. Additionally, LT-IIb and LT-IIc induced distinct differences in the profiles of the Ag-specific CD8+ T cell responses. While LT-IIc stimulated a robust and rapid primary CD8+ T cell response, LT-IIb exhibited slower CD8+ T cell expansion and contraction kinetics with the formation of higher percentages of effector memory cells. In comparison to LT-I and LT-IIc, LT-IIb evoked better long-term protection after immunization. Furthermore, LT-IIb and LT-IIc enhanced the total number of dendritic cells (DC) in the draining lymph node (DLN) and expression of costimulatory molecules CD80, CD86, and CD40 on DCs. In contrast to LT-I, LT-IIb and LT-IIc induced less edema, cellular infiltrates, and general inflammation at the site of ID injection. Thus, LT-IIb and LT-IIc are attractive comprehensive ID adjuvants with unique characteristic that enhance humoral and cellular immunity to a co-administered protein Ag.
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影响因子：
3.1
作者：
Nawar, Hesham F.;King-Lyons, Natalie D.;Connell, Terry D.
通讯作者：
Connell, Terry D.
影响因子：
168.9
作者：
Levine, Orin S.;Bloom, David E.;Greenwood, Brian
通讯作者：
Greenwood, Brian
影响因子：
3.7
作者：
Greene, Christopher J.;Chadwick, Chrystal M.;Connell, Terry D.
通讯作者：
Connell, Terry D.
影响因子：
4.4
作者：
Foulds, KE;Zenewicz, LA;Shen, H
通讯作者：
Shen, H
影响因子：
5.5
作者：
Calabro, Samuele;Tortoli, Marco;Wack, Andreas
通讯作者：
Wack, Andreas