Long-lasting T cell responses to biological warfare Vaccines in human vaccinees

Long-lasting T cell responses to biological warfare Vaccines in human vaccinees
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DOI:
10.1086/504806
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发表时间:
2006-07-01
影响因子:
11.8
通讯作者:
Peakman, Mark
Peakman, Mark
中科院分区:
医学1区
文献类型:
--
作者:
Allen, Jennifer S.;Skowera, Ania;Peakman, Mark

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背景。针对生物战的医疗对策包括使用炭疽和鼠疫疫苗,这些疫苗需要反复给药和佐剂,以充分保护免受吸入性炭疽和肺鼠疫等威胁。尽管在最近的军事部署准备中广泛使用了这些措施,但与百日咳或破伤风-白喉疫苗等传统疫苗相比,对这些疫苗诱导的细胞介导免疫反应知之甚少。为了研究这个问题,我们使用细胞因子酶联免疫斑点法测定了1990-1991年海湾战争期间接种过疫苗的军人体内产生干扰素- γ、白细胞介素-2、白细胞介素-4和白细胞介素-13的细胞。我们的数据表明,在接种炭疽和鼠疫疫苗12-15年后,血液循环中存在抗原特异性T细胞召回反应,其强度与破伤风-白喉类毒素相当。对炭疽的回忆反应是1型T辅助细胞(干扰素- γ和IL-2)和2型T辅助细胞(主要是IL-13)反应的大致相等的混合物,而鼠疫细胞免疫则更倾向于1型T辅助细胞反应。应答细胞的频率和类型与传统的破伤风-白喉(混合1型和2型T辅助细胞)疫苗相似。当退伍军人根据是否报告多症状性疾病进行分组时,虽然每组的病例数较少,但细胞反应的频率和类型没有差异,这些数据应被解释为初步数据。这项研究表明,尽管炭疽和鼠疫疫苗在实现保护性宿主免疫方面存在任何假定的局限性,但这些病原体可产生持久的细胞介导反应。
Background. Medical countermeasures against biological warfare include the use of vaccines for anthrax and plague, which require repeated dosing and adjuvant to achieve adequate protection from threats such as inhalational anthrax and pneumonic plague. Despite the widespread use of these measures in preparation for recent military deployments, little is known about the cell-mediated immune response that is induced by these vaccines, in comparison with conventional vaccines, such as pertussis or tetanus-diphtheria vaccines.Methods. To examine this question, we used cytokine enzyme-linked immunospot assays to measure interferon-gamma, interleukin ( IL)-2, IL-4, and IL-13-producing cells in military service personnel vaccinated during the Gulf War of 1990-1991.Results. Our data indicate that 12-15 years after vaccination against anthrax and plague, antigen-specific T cell recall responses are present in the circulation and are comparable in magnitude to those for tetanus-diphtheria toxoids. Recall responses to anthrax were an approximately equal mixture of type 1 T helper cell ( interferon-gamma and IL-2) and type 2 T helper cell ( predominantly IL-13) responses, whereas plague cellular immunity was more polarized toward type 1 T helper cell responses. Responder cell frequency and type were similar to that against conventional tetanus-diphtheria ( mixed type 1 and type 2 T helper cells) vaccine. When veterans were divided according to whether or not they reported multisymptom-illness, there was no difference in the frequency or type of cellular response, although the number of cases in each group was small, and these data should be interpreted as preliminary.Conclusions. This study shows that, despite any putative limitations of vaccines for anthrax and plague in terms of achieving protective host immunity, long-lasting cell-mediated responses are generated with these agents.