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

描述(申请人提供)：肺炎是美国住院和死亡的主要传染病原因。肺炎链球菌是肺炎的主要致病菌。2000年，美国婴儿接种计划中引入了七价肺炎球菌结合疫苗(PCV7)，大大降低了2岁以下儿童侵袭性肺炎和肺炎的发病率。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。在未接种疫苗的受试者中肺炎球菌疾病的发病率同时下降，这为通过减少这种传播进行间接保护提供了强有力的证据。虽然在普通人群中观察到非疫苗血清型(即替换)引起的肺炎球菌疾病的发病率略有增加，但在肺炎球菌疾病的高危情况下观察到更强烈的替换。2010年，13价肺炎球菌结合疫苗(PCV13)取代了婴儿接种计划中的PCV7。这种新疫苗的推出是为了预防大部分仍然严重的IPD，包括替换性疾病，这在很大程度上是由于PCV13中包括的另外6种血清型。2011年12月，FDA仅根据免疫原性数据批准PCV13在50岁以上的成年人中使用。然而，关于在成人中使用PCV13的正式国家建议已被推迟，直到获得关于PCV13对临床结果的影响以及未接种组中婴儿疫苗接种计划的间接影响的更多信息。来自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，在未接种疫苗的成年人中也注意到类似的下降。然而，与肺炎球菌肺炎相比，IPD是罕见的，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发病率有实质性影响尚不清楚。如果为婴儿接种PCV13疫苗已经在未接种疫苗的成年人中产生了实质性的间接好处，那么新的成人疫苗接种计划的潜在有效性可能会受到很大限制。此外，是否已向肺炎球菌疾病高危状况的成年人提供间接保护仍不清楚。我们建议进行一系列研究，具体目的如下：1)测试常规接种PCV13疫苗会导致未接种PCV13的儿童和成人肺炎住院人数下降的假设；以及2)测试常规接种PCV13婴儿可减少肺炎肺炎住院人数的假设，这些成人具有肺炎球菌感染的高危条件。评估PCV13婴儿疫苗接种计划的间接效果是制定肺炎球菌疫苗接种政策的关键一步。

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.