Interleukin-12 is produced by macrophages in response to live or killed Bordetella pertussis and enhances the efficacy of an acellular pertussis vaccine by promoting induction of Th1 cells
Interleukin-12 is produced by macrophages in response to live or killed Bordetella pertussis and enhances the efficacy of an acellular pertussis vaccine by promoting induction of Th1 cells
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DOI：
10.1128/iai.64.12.5295-5301.1996
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发表时间：
1996-12-01
影响因子：
3.1
通讯作者：
Mills, KHG
中科院分区：
文献类型：
--
作者：
Mahon, BP;Ryan, MS;Mills, KHG
使用小鼠呼吸道感染模型，我们先前已经证明，感染百日咳杆菌或全细胞百日咳疫苗免疫可诱导抗原特异性Th1细胞，从而对气溶胶攻击提供高水平的保护。相比之下，由百日咳杆菌解毒毒素、丝状血凝素和吸附在明矾上的百日咳杆菌凝集素组成的无细胞疫苗免疫会产生Th2细胞，并与攻击后细菌清除延迟有关。在这项研究中，我们证明了在体外或体内添加白细胞介素12(IL-12)可以增强脱细胞疫苗诱导的1型T细胞细胞因子反应。此外，在联合注射IL-12和无细胞疫苗的小鼠中，细菌清除率与用有效的全细胞疫苗免疫后观察到的相似。对小鼠巨噬细胞分泌IL-12的分析表明，这种细胞因子是在百日咳杆菌感染或全细胞疫苗免疫后体内产生的。经百日咳活菌感染或热灭活百日咳杆菌或百日咳杆菌脂多糖刺激后，肺、脾和腹膜巨噬细胞上清液中均可检测到IL-12。相比之下，用无细胞疫苗的细菌抗原丝状血凝素、解毒百日咳毒素和Pertactin刺激巨噬细胞后，不能检测到IL-12。我们的研究结果表明，内源性IL-12的诱导可能有助于百日咳全细胞疫苗的高效性，并表明使用含有IL-12作为佐剂的低反应性无细胞疫苗有可能获得这种高水平的保护。
Using a murine respiratory infection model, we have demonstrated previously that infection with Bordetella pertussis or immunization with a whole-cell pertussis vaccine induced antigen-specific Th1 cells, which conferred a high level of protection against aerosol challenge. In contrast, immunization with an acellular vaccine, consisting of the B. pertussis components detoxified pertussis toxin, filamentous hemagglutinin, and pertactin adsorbed to alum, generated Th2 cells and was associated with delayed bacterial clearance following challenge. In this study, we demonstrated that addition of interleukin-12 (IL-12) either in vitro or in vivo enhanced type 1 T-cell cytokine responses induced with an acellular vaccine. Furthermore, the rate of bacterial clearance in mice coinjected with IL-12 and the acellular vaccine was similar to that observed following immunization with a potent whole-cell vaccine. Analysis of IL-12 secretion by murine macrophages suggested that this cytokine is produced in vivo following B. pertussis infection or immunization with the whole-cell vaccine. IL-12 was detected in the supernatants of lung, splenic, and peritoneal macrophages infected with live B. pertussis or stimulated with heat-killed whole B. pertussis or B. pertussis lipopolysaccharide. In contrast, IL-12 could not be detected following stimulation of macrophages with the bacterial antigens filamentous hemagglutinin, detoxified pertussis toxin, and pertactin, the components of acellular vaccines. Our findings suggest that induction of endogenous IL-12 may contribute to the high efficacy of pertussis whole-cell vaccines and also demonstrate that it is possible to attain these high levels of protection with a less reactogenic acellular vaccine incorporating IL-12 as an adjuvant.