■世界卫生组织推荐给婴儿接种肺炎球菌结合疫苗。关于不同肺炎球菌疫苗的免疫原性和功效差异的证据参差不齐。
主要目的是比较肺炎球菌结合疫苗-10与肺炎球菌结合疫苗-13的免疫原性。主要次要目的是比较肺炎球菌结合疫苗-10与肺炎球菌结合疫苗-13的血清功效。
■我们搜索了Cochrane图书馆,EMBASE,全球卫生,MEDLINE,ClinicalTrials.gov和试验搜索。谁。截至2022年7月。如果在2岁以下儿童的随机试验中直接比较肺炎球菌结合疫苗-7,肺炎球菌结合疫苗-10或肺炎球菌结合疫苗-13,则研究合格。并提供了至少一个时间点的免疫原性数据。请求个体参与者数据,否则使用汇总数据。结果包括血清型特异性免疫球蛋白G的几何平均比率和血清感染的相对风险。血清感染定义为每个个体在初次疫苗接种后系列时间点和加强剂量之间的抗体升高。推测亚临床感染的证据。分析每个试验以获得几何平均值的比率的对数及其标准误差。通过比较疫苗组之间血清感染的参与者比例来估计血清感染的相对风险(“血清功效”)。对数几何平均比率,对数相对风险及其标准误差构成了证据综合的输入数据。对于所有三种疫苗中含有的血清型,可以使用网络荟萃分析来综合证据。对于其他血清型,使用荟萃分析。将血清功效分析的结果纳入肺炎球菌传播动力学的数学模型,以比较肺炎球菌结合疫苗10和肺炎球菌结合疫苗13引入对侵袭性肺炎球菌疾病病例的不同影响。该模型估计了疫苗引入25年的影响,并进行了经济评估。
■总共,来自38个国家的47项研究合格。28项和12项具有可用数据的研究包括在免疫原性和血清功效分析中,分别。在初次疫苗接种系列后1个月,比较肺炎球菌结合疫苗13与肺炎球菌结合疫苗10对血清型4,9V和23F的肺炎球菌结合疫苗13的几何平均值比,肺炎球菌结合疫苗-13的免疫球蛋白G应答显著高于1.14至1.54倍。对于血清型4,6B的肺炎球菌结合疫苗-13,在加强剂量之前血清感染的风险较低,9V,18C和23F比肺炎球菌缀合物疫苗-10。大多数血清型和两种结果均存在显着的异质性和不一致性。初次疫苗接种后两倍高的抗体与血清感染风险降低54%相关(相对风险0.46,95%置信区间0.23至0.96)。在建模的场景中,2006年引入的肺炎球菌结合疫苗-13或肺炎球菌结合疫苗-10导致肺炎球菌结合疫苗-10的病例减少的速度低于肺炎球菌结合疫苗-13。与肺炎球菌结合疫苗-10相比,肺炎球菌结合疫苗-13计划预计在2006年至2030年之间避免额外的2808例(95%置信区间2690至2925)侵袭性肺炎球菌疾病病例。
分析使用婴儿疫苗研究的数据,并在加强剂量之前采集血液样本。将加强前功效外推到加强后时间点的影响是未知的。网络荟萃分析模型包含显著的异质性,这可能导致偏差。
■在肺炎球菌结合疫苗-13和肺炎球菌结合疫苗-10之间的免疫原性和血清效力中发现血清型特异性差异。疫苗接种后较高的抗体反应与随后感染的较低风险相关。这些方法可用于比较肺炎球菌结合疫苗并优化疫苗接种策略。为了将来的工作,可以确定其他肺炎球菌疫苗的血清功效估计值,这可能有助于新肺炎球菌疫苗的许可或政策决定。
■本研究注册为PROSPEROCRD42019124580。
■该奖项由美国国家卫生与护理研究所(NIHR)卫生技术评估计划(NIHR奖编号:17/148/03)资助,并在《卫生技术评估》中全文发布。28号34.有关更多奖项信息,请参阅NIHR资助和奖励网站。
肺炎球菌病是由细菌感染引起的可导致死亡的严重疾病。英国的儿童接种了预防这种疾病的疫苗,可以预防13种不同类型的肺炎球菌疾病。它非常有效,但是其他疫苗也是可用的,例如含有10种肺炎球菌疾病的。英国的疫苗是由政府购买的,选择提供哪种疫苗是基于疫苗的成本以及对我们健康的好处。然而,很少有信息比较不同的疫苗,人们通常认为它们是相同的。我们进行了一项大型分析,结合了两种主要许可的肺炎球菌疫苗的所有研究,以确定哪种疫苗提供了更好的感染保护,以及这如何影响成本。我们使用了医学期刊上发表的研究信息,以及拥有疫苗的公司所做的研究数据。我们的结果表明,对于两种疫苗中包含的10种血清型中的5种,肺炎球菌结合疫苗13比肺炎球菌结合疫苗10提供了更好的保护。当我们使用这些结果来模拟2006年英国疫苗接种计划中的任何一种疫苗可能发生的情况时,我们发现两种疫苗都导致疾病数量迅速减少,但是肺炎球菌结合疫苗-13比肺炎球菌结合疫苗-10的疾病减少更快。与肺炎球菌结合疫苗10相比,肺炎球菌结合疫苗13在25年的时间范围内预防了2808例疾病。我们的方法可用于比较其他疫苗,我们建议将来在决定疫苗产品选择时进行此类研究。
UNASSIGNED: Vaccination of infants with pneumococcal conjugate vaccines is recommended by the World Health Organization. Evidence is mixed regarding the differences in immunogenicity and efficacy of the different pneumococcal vaccines.
UNASSIGNED: The primary objective was to compare the immunogenicity of pneumococcal conjugate vaccine-10 versus pneumococcal conjugate vaccine-13. The main secondary objective was to compare the seroefficacy of pneumococcal conjugate vaccine-10 versus pneumococcal conjugate vaccine-13.
UNASSIGNED: We searched the Cochrane Library, EMBASE, Global Health, MEDLINE, ClinicalTrials.gov and trialsearch.who.int up to July 2022. Studies were eligible if they directly compared either pneumococcal conjugate vaccine-7, pneumococcal conjugate vaccine-10 or pneumococcal conjugate vaccine-13 in randomised trials of children under 2 years of age, and provided immunogenicity data for at least one time point. Individual participant data were requested and aggregate data used otherwise. Outcomes included the geometric mean ratio of serotype-specific immunoglobulin G and the relative risk of seroinfection. Seroinfection was defined for each individual as a rise in antibody between the post-primary vaccination series time point and the booster dose, evidence of presumed subclinical infection. Each trial was analysed to obtain the log of the ratio of geometric means and its standard error. The relative risk of seroinfection (\'seroefficacy\') was estimated by comparing the proportion of participants with seroinfection between vaccine groups. The log-geometric mean ratios, log-relative risks and their standard errors constituted the input data for evidence synthesis. For serotypes contained in all three vaccines, evidence could be synthesised using a network meta-analysis. For other serotypes, meta-analysis was used. Results from seroefficacy analyses were incorporated into a mathematical model of pneumococcal transmission dynamics to compare the differential impact of pneumococcal conjugate vaccine-10 and pneumococcal conjugate vaccine-13 introduction on invasive pneumococcal disease cases. The model estimated the impact of vaccine introduction over a 25-year time period and an economic evaluation was conducted.
UNASSIGNED: In total, 47 studies were eligible from 38 countries. Twenty-eight and 12 studies with data available were included in immunogenicity and seroefficacy analyses, respectively. Geometric mean ratios comparing pneumococcal conjugate vaccine-13 versus pneumococcal conjugate vaccine-10 favoured pneumococcal conjugate vaccine-13 for serotypes 4, 9V and 23F at 1 month after primary vaccination series, with 1.14- to 1.54-fold significantly higher immunoglobulin G responses with pneumococcal conjugate vaccine-13. Risk of seroinfection prior to the time of booster dose was lower for pneumococcal conjugate vaccine-13 for serotype 4, 6B, 9V, 18C and 23F than for pneumococcal conjugate vaccine-10. Significant heterogeneity and inconsistency were present for most serotypes and for both outcomes. Twofold higher antibody after primary vaccination was associated with a 54% decrease in risk of seroinfection (relative risk 0.46, 95% confidence interval 0.23 to 0.96). In modelled scenarios, pneumococcal conjugate vaccine-13 or pneumococcal conjugate vaccine-10 introduction in 2006 resulted in a reduction in cases that was less rapid for pneumococcal conjugate vaccine-10 than for pneumococcal conjugate vaccine-13. The pneumococcal conjugate vaccine-13 programme was predicted to avoid an additional 2808 (95% confidence interval 2690 to 2925) cases of invasive pneumococcal disease compared with pneumococcal conjugate vaccine-10 introduction between 2006 and 2030.
UNASSIGNED: Analyses used data from infant vaccine studies with blood samples taken prior to a booster dose. The impact of extrapolating pre-booster efficacy to post-booster time points is unknown. Network meta-analysis models contained significant heterogeneity which may lead to bias.
UNASSIGNED: Serotype-specific differences were found in immunogenicity and seroefficacy between pneumococcal conjugate vaccine-13 and pneumococcal conjugate vaccine-10. Higher antibody response after vaccination was associated with a lower risk of subsequent infection. These methods can be used to compare the pneumococcal conjugate vaccines and optimise vaccination strategies. For future work, seroefficacy estimates can be determined for other pneumococcal vaccines, which could contribute to licensing or policy decisions for new pneumococcal vaccines.
UNASSIGNED: This study is registered as PROSPERO CRD42019124580.
UNASSIGNED: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/148/03) and is published in full in Health Technology Assessment; Vol. 28, No. 34. See the NIHR Funding and Awards website for further award information.
Pneumococcal disease is a serious illness caused by a bacterial infection that can result in death. Children in the United Kingdom receive a vaccine to prevent this disease that protects against 13 different types of pneumococcal diseases. It is very effective, but other vaccines are also available, such as one that contains 10 types of pneumococcal diseases. Vaccines in the United Kingdom are bought by the government and the choice of which vaccine to provide is based on the cost of the vaccine as well as the benefits to our health. However, there is very little information comparing different vaccines and it is often assumed they are the same. We did a large analysis combining all studies of the two main licensed pneumococcal vaccines to determine which vaccine provides better protection against infection and how this affects costs. We used information from studies published in medical journals, and also data from studies done by the companies that own the vaccines. Our results showed that pneumococcal conjugate vaccine-13 vaccine provided better protection than pneumococcal conjugate vaccine-10 for 5 of the 10 serotypes that are contained in both vaccines. When we used these results to model what might have happened had either of these vaccines been introduced into the United Kingdom vaccination programme in 2006, we found that both vaccines caused a rapid decrease in the amount of disease, but that the decrease in disease was faster with pneumococcal conjugate vaccine-13 than pneumococcal conjugate vaccine-10. This resulted in 2808 cases of diseases prevented over a 25-year time frame with pneumococcal conjugate vaccine-13 compared with pneumococcal conjugate vaccine-10. Our methods can be used to compare other vaccines and we recommend this type of study be done in future when making decisions on vaccine product choice.