Fast Tracking the Vaccine Licensure Process to Control an Epidemic of Serogroup B Meningococcal Disease in New Zealand
Fast Tracking the Vaccine Licensure Process to Control an Epidemic of Serogroup B Meningococcal Disease in New Zealand
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DOI：
10.1086/603552
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发表时间：
2009-08-15
影响因子：
11.8
通讯作者：
Reid, Stewart
中科院分区：
文献类型：
--
作者：
Lennon, Diana;Jackson, Catherine;Reid, Stewart
B群脑膜炎双球菌疾病的流行是罕见的。尚未上市的毒株特异性外膜囊泡疫苗是目前唯一的控制工具。保护之间的相关性没有明确的定义，但公布的数据表明，测量的血清杀菌抗体水平与疗效平行。即使是婴儿也可以对菌株特异性疫苗产生菌株特异性抗体反应。新西兰的疫情(1991-2007年；高峰期[2001年]，每100,000人中有17.4例)主要由一种病毒株主导。经过5年(1996-2001年)对毒株特异性外膜泡囊疫苗制造商的搜索，一项快速研究计划(2002-2004年)在成人试验后确定了疫苗在婴儿(2个年龄组：6-10周和6-8个月)、儿童(16-24个月)和学龄儿童(8-12岁)中的安全性和免疫原性。与对照疫苗(脑膜炎球菌C结合疫苗和常规婴儿疫苗)相比，该疫苗具有反应性，但保留率较高。三种疫苗剂量产生的抗体水平(通过血清杀菌试验测量)被认为足以进行公共卫生干预。然而，在年轻婴儿中，需要第四剂才能达到与其他年龄段相同的水平。新西兰MedSafe的临时许可证基于血清学标准，这些标准得到了来自母体外膜泡囊疫苗研究的桥接安全数据的强化，对制造质量的独立评估，以及许可证获得后的安全监测和有效性评估的明确计划。
Epidemics of serogroup B meningococcal disease are rare. Strain-specific outer membrane vesicle vaccines, which are not marketed, are the only current tool for control. A correlate of protection is ill defined, but published data suggest that measured serum bactericidal antibody levels parallel efficacy. Even infants can mount a strain-specific antibody response to a strain-specific vaccine. New Zealand's epidemic (1991-2007; peak rate [in 2001], 17.4 cases per 100,000 persons) was dominated by a single strain. After a 5-year search (1996-2001) for a manufacturer for a strain-specific outer membrane vesicle vaccine, a fast-tracked research program (2002-2004) determined the safety and immunogenicity of vaccine in infants (2 age groups: 6-10 weeks and 6-8 months), children (age, 16-24 months), and school-aged children (age, 8-12 years) after an adult trial. The vaccine was reactogenic, compared with control vaccines (meningococcal C conjugate and routine infant vaccines), but retention was high. Three vaccine doses produced antibody levels (measured by serum bactericidal assay) that were considered to be adequate for public health intervention. However, in young infants, a fourth dose was required to achieve levels equivalent to those achieved by other age groups. Provisional licensure by New Zealand's MedSafe was based on serological criteria strengthened by bridged safety data from studies of the parent outer membrane vesicle vaccine, independent assessment of manufacturing quality, and a clear plan for safety monitoring and effectiveness evaluation after licensure.