Zuercher A W, Imboden M A, Jampen S, Bosse D, Ulrich M, Chtioui H, Lauterburg B H, Lang A B
Berna Biotech Ltd, Berne, Switzerland.
Clin Exp Immunol. 2006 Jan;143(1):132-8. doi: 10.1111/j.1365-2249.2005.02964.x.
Humoral immunity in response to an octavalent O-polysaccharide-toxin A conjugate Pseudomonas aeruginosa vaccine is well studied, and a phase III clinical study in cystic fibrosis (CF) patients is currently ongoing. In contrast, little is known about cellular immunity induced by this vaccine. Fifteen healthy volunteers were immunized on days 1 and 60. Parameters of cellular immunity were studied before vaccination on day 1, and on day 74. Analyses included flow cytometry of whole blood and antigen-induced proliferation of and cytokine production by lymphocyte cultures. The effects of immunization on the composition of peripheral blood lymphocytes as determined by flow cytometry were minor. In contrast, after immunization a highly significant increase of proliferation in response to stimulation with detoxified toxin A was noted: the stimulation index rose from 1.4 on day 1 to 42.2 on day 74 (restimulation with 0.4 microg/ml; P = 0.003). Immunization led to significant production of interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha by antigen-stimulated lymphocytes. In contrast, no significant induction of interleukin (IL)-4 or IL-10 was observed. In conclusion, immunization of healthy volunteers led to activation of cellular immunity including strong antigen-specific proliferation and cytokine production. In CF patients priming of the cellular immune system towards a Th1-like pattern would be of potential advantage. Therefore, confirmatory analyses in immunized CF patients with and without chronic infection with P. aeruginosa are foreseen.
针对八价O-多糖-毒素A结合型铜绿假单胞菌疫苗的体液免疫已得到充分研究，目前一项针对囊性纤维化（CF）患者的III期临床研究正在进行。相比之下，对于该疫苗诱导的细胞免疫知之甚少。15名健康志愿者在第1天和第60天进行了免疫接种。在第1天接种疫苗前和第74天研究了细胞免疫参数。分析包括全血的流式细胞术以及淋巴细胞培养物中抗原诱导的增殖和细胞因子产生。通过流式细胞术测定，免疫接种对外周血淋巴细胞组成的影响较小。相比之下，免疫接种后，发现用解毒毒素A刺激后的增殖显著增加：刺激指数从第1天的1.4上升至第74天的42.2（用0.4μg/ml再次刺激；P = 0.003）。免疫接种导致抗原刺激的淋巴细胞显著产生干扰素（IFN）-γ和肿瘤坏死因子（TNF）-α。相比之下，未观察到白细胞介素（IL）-4或IL-10的显著诱导。总之，健康志愿者的免疫接种导致细胞免疫激活，包括强烈的抗原特异性增殖和细胞因子产生。在CF患者中，将细胞免疫系统引导至类似Th1的模式可能具有潜在优势。因此，预计将对接种疫苗的有或无铜绿假单胞菌慢性感染的CF患者进行验证性分析。
