The Impact of Infant Vaccination with a 13-valent Pneumococcal Conjugate Vaccine

婴儿接种 13 价肺炎球菌结合疫苗的影响

• 批准号: 8702459
• 负责人: CARLOS G GRIJALVA
• 金额: $ 5万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8702459
• 关键词: Impact; Infant; Vaccination; 13; valent

DESCRIPTION (provided by applicant): Pneumonia is the leading infectious cause of hospitalization and death in the United States (US). Streptococcus pneumoniae is the main bacterial cause of pneumonia. The introduction of a seven-valent pneumococcal conjugate vaccine (PCV7) into the US infant vaccination schedule in 2000 led to substantial reductions in the incidence of invasive pneumococcal disease (IPD) and pneumonia in children <2 years. By preventing nasopharyngeal colonization with pneumococcal vaccine serotypes, PCV7 also interfered with the transmission of bacteria from person to person. Concurrent declines in the incidence of pneumococcal diseases among unvaccinated subjects provided strong evidence for indirect protection through reduction of such transmission. Although modest increases in the incidence of pneumococcal diseases caused by non- vaccine serotypes (i.e. replacement) was observed in the general population, a more intense replacement was observed among persons with high-risk conditions for pneumococcal diseases. A 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the infant vaccination schedule in 2010. This new vaccine was introduced to prevent a large portion of remaining serious IPD, including replacement disease, much of which is due to the 6 additional serotypes included in PCV13. In December 2011, FDA approved PCV13 for use among adults aged e50 years, based on immunogenicity data only. However, formal national recommendation for its use in adults has been postponed until additional information on the effects of PCV13 on clinical outcomes and the indirect effects of the infant vaccination program in unvaccinated groups become available. Preliminary data from surveillance systems suggest that IPD caused by the 6 additional PCV13 serotypes has started to decline in young children, and similar reductions have been noted among unvaccinated adults. Nevertheless, IPD is rare compared with pneumococcal pneumonia, a major driver of the vaccine cost- effectiveness. Whether routine vaccination of infants with PCV13 has a substantial impact on the incidence of pneumonia in unvaccinated subjects is unknown. If vaccination of infants with PCV13 has already resulted in substantial indirect benefits among unvaccinated adults, then the potential effectiveness of a new adult vaccination program may be substantially limited. Moreover, whether indirect protection has been conferred to adults with high-risk conditions for pneumococcal diseases remains unclear. We propose to conduct a series of studies with the following specific aims: 1) Test the hypothesis that routine vaccination of infants with PCV13 resulted in declines in pneumonia hospitalizations among unvaccinated children and adults; and, 2) Test the hypothesis that routine vaccination of infants with PCV13 reduced pneumonia hospitalizations among unvaccinated adults with high-risk conditions for pneumococcal infections. The evaluation of the indirect effects of the PCV13 infant vaccination program is a critical step for the formulation of pneumococcal vaccination policies.

描述（由申请人提供）：肺炎是美国 (US) 住院和死亡的主要原因。肺炎链球菌是引起肺炎的主要细菌。 2000 年，美国婴儿疫苗接种计划中引入了七价肺炎球菌结合疫苗 (PCV7)，导致 2 岁以下儿童侵袭性肺炎球菌疾病 (IPD) 和肺炎的发病率大幅下降。通过防止肺炎球菌疫苗血清型在鼻咽部定植，PCV7 还干扰了细菌在人与人之间的传播。未接种疫苗的受试者中肺炎球菌疾病发病率的同时下降为通过减少此类传播提供间接保护提供了强有力的证据。尽管在普通人群中观察到由非疫苗血清型（即替代）引起的肺炎球菌疾病的发病率略有增加，但在肺炎球菌疾病高危人群中观察到更强烈的替代。 2010 年，13 价肺炎球菌结合疫苗 (PCV13) 取代了婴儿疫苗接种计划中的 PCV7。这种新疫苗的推出是为了预防大部分剩余的严重 IPD，包括替代性疾病，其中大部分是由于 PCV13 中包含的 6 种额外血清型所致。 2011 年 12 月，FDA 仅根据免疫原性数据批准 PCV13 在 50 岁以下成年人中使用。然而，在获得有关 PCV13 对临床结果的影响以及婴儿疫苗接种计划对未接种疫苗群体的间接影响的更多信息之前，关于在成人中使用该疫苗的正式国家建议已被推迟。监测系统的初步数据表明，由另外 6 种 PCV13 血清型引起的 IPD 在幼儿中已开始下降，在未接种疫苗的成人中也出现了类似的下降。然而，与肺炎球菌肺炎相比，IPD 很少见，而肺炎球菌肺炎是疫苗成本效益的主要驱动因素。婴儿常规接种 PCV13 疫苗是否对未接种疫苗的受试者肺炎的发病率有重大影响尚不清楚。如果婴儿接种 PCV13 疫苗已经给未接种疫苗的成年人带来了实质性的间接益处，那么新的成人疫苗接种计划的潜在效果可能会受到很大限制。此外，是否为肺炎球菌疾病高危成年人提供了间接保护仍不清楚。我们建议开展一系列具有以下具体目标的研究：1）检验以下假设：对婴儿进行常规疫苗接种 PCV13 可以减少未接种疫苗的儿童和成人的肺炎住院率； 2) 检验以下假设：对婴儿进行 PCV13 常规疫苗接种可减少患有肺炎球菌感染高危状况的未接种疫苗成人的肺炎住院治疗。 PCV13婴儿疫苗接种计划的间接影响评估是制定肺炎球菌疫苗接种政策的关键步骤。