A murine model in which protection correlates with pertussis vaccine efficacy in children reveals complementary roles for humoral and cell-mediated immunity in protection against Bordetella pertussis
A murine model in which protection correlates with pertussis vaccine efficacy in children reveals complementary roles for humoral and cell-mediated immunity in protection against Bordetella pertussis
复制标题
DOI：
10.1128/iai.66.2.594-602.1998
复制
发表时间：
1998-02-01
影响因子：
3.1
通讯作者：
Mahon, BP
中科院分区：
文献类型：
--
作者：
Mills, KHG;Ryan, M;Mahon, BP
3期疗效试验的结果表明，无细胞和全细胞百日咳疫苗可以提供针对百日咳的保护，然而，尽管疫苗开发取得了进展，但临床试验尚未提供关于针对百日咳博德特氏菌的保护性免疫机制的重要新信息，基于测量对单个抗原的抗体应答的经典方法未能定义保护的免疫学相关性，一个可靠的动物模型，预测无细胞和全细胞百日咳疫苗在儿童中的效力，将有助于阐明对B的免疫保护机制。这将有助于百日咳疫苗的监管和未来开发。在这项研究中，我们已经表明，B。免疫小鼠呼吸道激发后百日咳清除率与儿童疫苗效力相关，使用该模型与γ干扰素靶向干扰的小鼠一起使用（IFN-γ）受体、白细胞介素-4或免疫球蛋白重链基因，我们已经证明了B细胞或其产物在细菌清除中的绝对需要以及IFN-γ的作用。被动免疫实验的结果表明，无细胞百日咳疫苗免疫后早期的保护作用是由针对多种保护性抗原的抗体介导的，相反，由先前感染或用全细胞百日咳疫苗免疫所赋予的更完全的保护反映了Th 1细胞的诱导。我们的研究结果表明，免疫机制对B，百日咳涉及体液和细胞免疫反应，这不是针对一个单一的保护性抗原，从而提供了一个解释以前的失败，以确定一个免疫相关的保护。
The results of phase 3 efficacy trials have shown that acellular and whole-cell pertussis vaccines can confer protection against whooping cough, However, despite the advances in vaccine development, clinical trials have not provided significant new information on the mechanism of protective immunity against Bordetella pertussis, Classical approaches based on measurement of antibody responses to individual antigens failed to define an immunological correlate of protection, A reliable animal model, predictive of acellular and whole-cell pertussis vaccine potency in children, would facilitate an elucidation of the mechanism of immune protection against B. pertussis and would assist in the regulatory control and future development of pertussis vaccines. In this study, we have shown that the rate of B. pertussis clearance following respiratory challenge of immunized mice correlated with vaccine efficacy in children, Using this model together with mice with targeted disruptions of the gamma interferon (IFN-gamma) receptor, interleukin-4 or immunoglobulin heavy-chain genes, we have demonstrated an absolute requirement for B cells or their products in bacterial clearance and a role for IFN-gamma in immunity generated by previous infection or immunization with the whole-cell pertussis vaccine, The results of passive immunization experiments suggested that protection early after immunization with acellular pertussis vaccines is mediated by antibody against multiple protective antigens, In contrast, more complete protection conferred by previous infection or immunization with whole-cell pertussis vaccines reflected the induction of Th1 cells. Our findings suggest that the mechanism of immunity against B, pertussis involves humoral and cellular immune responses which are not directed against a single protective antigen and thus provide an explanation for previous failures to define an immunological correlate of protection.