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

描述（由申请人提供）：肺炎是美国（US）住院和死亡的主要传染性原因。肺炎链球菌是引起肺炎的主要细菌。2000年，美国婴儿接种计划中引入了七价肺炎球菌结合疫苗（PCV 7），导致2岁以下儿童侵袭性肺炎球菌病（IPD）和肺炎的发病率大幅下降。通过预防肺炎球菌疫苗血清型在鼻咽的定植，PCV 7也干扰了细菌在人与人之间的传播。同时，未接种疫苗的受试者中肺炎球菌疾病的发病率下降，为通过减少这种传播来间接保护提供了强有力的证据。虽然在一般人群中观察到非疫苗血清型（即替代）引起的肺炎球菌疾病发病率略有增加，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（PCV 13）取代了婴儿疫苗接种计划中的PCV 7。引入这种新疫苗是为了预防大部分剩余的严重IPD，包括替代病，其中大部分是由于PCV 13中包含的6种额外血清型。2011年12月，FDA仅基于免疫原性数据批准PCV 13用于50岁以上的成人。然而，正式的国家建议其在成人中使用已被推迟，直到更多的信息PCV 13对临床结果的影响和婴儿疫苗接种计划在未接种疫苗的群体中的间接影响变得可用。来自监测系统的初步数据表明，由另外6种PCV 13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PCV 13疫苗是否对未接种受试者的肺炎发病率有实质性影响尚不清楚。如果接种PCV 13的婴儿已经在未接种疫苗的成人中产生了大量的间接益处，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，是否已向患有肺炎球菌疾病高风险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，具体目标如下：1）检验婴儿常规接种PCV 13疫苗导致未接种疫苗的儿童和成人肺炎住院率下降的假设; 2）检验婴儿常规接种PCV 13疫苗减少未接种疫苗的肺炎球菌感染高危成人肺炎住院率的假设。评估PCV 13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步骤。

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.