Mucosal delivery switches the response to an adjuvanted tuberculosis vaccine from systemic TH1 to tissue-resident TH17 responses without impacting the protective efficacy.
Mucosal delivery switches the response to an adjuvanted tuberculosis vaccine from systemic TH1 to tissue-resident TH17 responses without impacting the protective efficacy.
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DOI：
10.1016/j.vaccine.2015.10.115
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发表时间：
2015-11-27
期刊：
影响因子：
5.5
通讯作者：
Coler RN
中科院分区：
文献类型：
--
作者：
Orr MT;Beebe EA;Hudson TE;Argilla D;Huang PW;Reese VA;Fox CB;Reed SG;Coler RN
尽管广泛使用卡介苗，肺结核仍是传染病死亡的主要原因之一。一些新的结核病疫苗已经进入临床评估，以取代或加强卡介苗，包括ID93+GLA-SE，一种佐剂亚单位疫苗。绝大多数正在试验的新结核病疫苗是非肠道注射的，尽管鼻内注射可以增强小动物模型中的肺部居民免疫力和保护效力。佐剂亚单位疫苗ID93+GLA-SE对小鼠和豚鼠的TH1免疫和对结核分枝杆菌的雾化免疫均有保护作用。在这里，我们描述了这种疫苗的免疫原性和效力，当给药时。鼻腔给药将CD4T细胞的应答从TH1切换到TH17主导的组织驻留应答，肺组织和肺表面ID93特异性细胞的频率增加。令人惊讶的是，这些变化并没有影响ID93+GLA-SE的保护效果。与肌肉免疫不同，ID93+GLA不需要角鲨烯水包油乳剂SE在鼻腔给药时诱导保护性的CD4T细胞。最后，我们证明了肿瘤坏死因子和白介素17受体对于鼻腔疫苗的有效性是必不可少的，并提出了另一种保护机制。
Pulmonary tuberculosis (TB) remains one of the leading causes of infectious disease death despite widespread usage of the BCG vaccine. A number of new TB vaccines have moved into clinical evaluation to replace or boost the BCG vaccine including ID93+GLA-SE, an adjuvanted subunit vaccine. The vast majority of new TB vaccines in trials are delivered parenterally even though intranasal delivery can augment lung-resident immunity and protective efficacy in small animal models. Parenteral immunization with the adjuvanted subunit vaccine ID93+GLA-SE elicits robust TH1 immunity and protection against aerosolized Mycobacterium tuberculosis in mice and guinea pigs. Here we describe the immunogenicity and efficacy of this vaccine when delivered intranasally. Intranasal delivery switches the CD4 T cell response from a TH1 to a TH17 dominated tissue-resident response with increased frequencies of ID93-specific cells in both the lung tissue and at the lung surface. Surprisingly these changes do not affect the protective efficacy of ID93+GLA-SE. Unlike intramuscular immunization, ID93+GLA does not require the squalene-based oil-in-water emulsion SE to elicit protective CD4 T cells when delivered intranasally. Finally we demonstrate that TNF and the IL-17 receptor are dispensable for the efficacy of the intranasal vaccine suggesting an alternative mechanism of protection.