Protection against tuberculosis with homologous or heterologous protein/vector vaccine approaches is not dependent on CD8+ T cells.
Protection against tuberculosis with homologous or heterologous protein/vector vaccine approaches is not dependent on CD8+ T cells.
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DOI：
10.4049/jimmunol.1301161
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发表时间：
2013-09-01
期刊：
影响因子：
--
通讯作者：
Coler RN
中科院分区：
文献类型：
--
作者：
Baldwin SL;Ching LK;Pine SO;Moutaftsi M;Lucas E;Vallur A;Orr MT;Bertholet S;Reed SG;Coler RN
已作出相当大的努力来开发结核分枝杆菌（Mtb）疫苗，以增强卡介苗或为那些不能接种卡介苗的人接种。我们假设CD4+和CD8+ T细胞反应与异源启动/增强疫苗方法可以诱导C57BL/6小鼠抗Mtb的长期疫苗效力。我们制作了一种表达ID93 （Ad5-ID93）的腺病毒载体，用于诱导CD8 T细胞与我们的候选结核（TB）疫苗ID93/GLA-SE一起使用，该疫苗可诱导强效Th1 CD4 T细胞。Ad5-ID93产生id93特异性CD8+ t细胞反应并诱导对Mtb的保护。当Ad5-ID93与ID93/GLA-SE一起以初始增强策略给药时，产生CD4+和CD8+ T细胞并提供对Mtb的保护。在MHC I类缺陷小鼠模型中，包括Ad5-ID93组在内的所有组都引起了抗原特异性CD4+ T细胞反应，抗原特异性CD8+ T细胞明显减少，但仍然对Mtb有保护作用，这表明CD4+ Th1 T细胞可以弥补CD8+ T细胞的损失。最后，异源免疫的顺序至关重要。只有在ID93/GLA-SE引物之后，以Ad5-ID93作为增强剂，才能观察到疫苗的长期保护作用。同源ID93/GLA-SE启动/增强方案也诱导了长期保护。这两种方法之间的保护关联之一是在最后一次免疫后6个月，产生id93特异性IFN-γ的CD4+ T细胞总数增加。我们的发现不仅为结核病疫苗的开发提供了思路，也为其他需要T细胞免疫的疾病提供了思路。
Considerable effort has been directed to develop Mycobacterium tuberculosis (Mtb) vaccines to boost BCG or for those who cannot be immunized with BCG. We hypothesized that CD4+ and CD8+ T cell responses with a heterologous prime/boost vaccine approach could induce long-lived vaccine efficacy against Mtb in C57BL/6 mice. We produced an adenovirus vector expressing ID93 (Ad5-ID93) for induction of CD8 T cells to use with our candidate tuberculosis (TB) vaccine, ID93/GLA-SE, which induces potent Th1 CD4 T cells. Ad5-ID93 generates ID93-specific CD8+ T-cell responses and induces protection against Mtb. When Ad5-ID93 is administered in a prime-boost strategy with ID93/GLA-SE, both CD4+ and CD8+ T cells are generated and provide protection against Mtb. In a MHC class I deficient mouse model, all groups including the Ad5-ID93 group elicited an antigen-specific CD4+ T-cell response and significantly fewer antigen-specific CD8+ T cells, but were still protected against Mtb, suggesting that CD4+ Th1 T cells could compensate for the loss of CD8+ T cells. Lastly, the order of the heterologous immunizations was critical. Long-lived vaccine protection was observed only when Ad5-ID93 was given as the boost following an ID93/GLA-SE prime. The homologous ID93/GLA-SE prime/boost regimen also induced long-lived protection. One of the correlates of protection between these two approaches was an increase in the total number of ID93-specific IFN-γ-producing CD4+ T cells six months following the last immunization. Our findings provide insight into the development of vaccines not only for tuberculosis but other diseases requiring T cell immunity.
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影响因子：
3.7
作者：
Magalhaes, Isabelle;Sizemore, Donata R.;Ahmed, Raija K.;Mueller, Stefanie;Wehlin, Lena;Scanga, Charles;Weichold, Frank;Schirru, Giulia;Pau, Maria Grazia;Goudsmit, Jaap;Kuhlmann-Berenzon, Sharon;Spangberg, Mats;Andersson, Jan;Gaines, Hans;Thorstensson, Rigmor;Skeiky, Yasir A. W.;Sadoff, Jerry;Maeurer, Markus
通讯作者：
Maeurer, Markus
MTB衍生的抗原对人CD8+ T细胞的HLA-E依赖性表现。
影响因子：
15.3
作者：
Heinzel, Amy S;Grotzke, Jeff E;Lines, Rebecca A;Lewinsohn, Deborah A;McNabb, Andria L;Streblow, Daniel N;Braud, Veronique M;Grieser, Heather J;Belisle, John T;Lewinsohn, David M
通讯作者：
Lewinsohn, David M
影响因子：
3.7
作者：
Koup RA;Roederer M;Lamoreaux L;Fischer J;Novik L;Nason MC;Larkin BD;Enama ME;Ledgerwood JE;Bailer RT;Mascola JR;Nabel GJ;Graham BS;VRC 009 Study Team;VRC 010 Study Team
通讯作者：
VRC 010 Study Team
DOI：
10.1093/cid/cis327
发表时间：
2012-07
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Lillie PJ;Berthoud TK;Powell TJ;Lambe T;Mullarkey C;Spencer AJ;Hamill M;Peng Y;Blais ME;Duncan CJ;Sheehy SH;Havelock T;Faust SN;Williams RL;Gilbert A;Oxford J;Dong T;Hill AV;Gilbert SC
通讯作者：
Gilbert SC
DOI：
10.4049/jimmunol.1200061
发表时间：
2013-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Green AM;Difazio R;Flynn JL
通讯作者：
Flynn JL