Odutola Aderonke, Ota Martin O C, Antonio Martin, Ogundare Ezra O, Saidu Yauba, Foster-Nyarko Ebenezer, Owiafe Patrick K, Ceesay Fatima, Worwui Archibald, Idoko Olubukola T, Owolabi Olumuyiwa, Bojang Abdoulie, Jarju Sheikh, Drammeh Isatou, Kampmann Beate, Greenwood Brian M, Alderson Mark, Traskine Magali, Devos Nathalie, Schoonbroodt Sonia, Swinnen Kristien, Verlant Vincent, Dobbelaere Kurt, Borys Dorota
Medical Research Council Unit, Vaccines & Immunity Theme, Banjul, Gambia.
Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.
Vaccine. 2017 May 2;35(19):2531-2542. doi: 10.1016/j.vaccine.2017.03.071. Epub 2017 Apr 4.
Conserved pneumococcal proteins are potential candidates for inclusion in vaccines against pneumococcal diseases. In the first part of a two-part study, an investigational vaccine (PHiD-CV/dPly/PhtD-30) containing 10 pneumococcal serotype-specific polysaccharide conjugates (10VT) combined with pneumolysin toxoid and pneumococcal histidine triad protein D (30μg each) was well tolerated by Gambian children. Part two, presented here, assessed the efficacy of two PHiD-CV/dPly/PhtD formulations against pneumococcal nasopharyngeal carriage (NPC) prevalence in infants.
In this phase 2, randomized, controlled, observer-blind trial, healthy infants aged 8-10weeks, recruited from a peri-urban health center, were randomized (1:1:1:1:1:1) into six groups. Four groups received PHiD-CV/dPly/PhtD (10 or 30μg of each protein), PHiD-CV, or 13-valent pneumococcal conjugate vaccine at ages 2-3-4months (3+0 infant schedule) and two groups PHiD-CV/dPly/PhtD-30 or PHiD-CV at 2-4-9months (2+1 infant schedule). The primary objective was impact on non-10VT NPC at ages 5-9-12months. Secondary objectives included confirmatory analysis of protein dose superiority and safety/reactogenicity. Impact on pneumococcal NPC acquisition, bacterial load, and ply and phtD gene sequencing were explored.
1200 infants were enrolled between June 2011 and May 2012. Prevalences of pneumococcal (60-67%) and non-10VT (55-61%) NPC were high at baseline. Across all post-vaccination time points, efficacy of PHiD-CV/dPly/PhtD-10 and PHiD-CV/dPly/PhtD-30 against non-10VT NPC (3+0 schedule) was 1.1% (95% CI -21.5, 19.5) and 2.1% (-20.3, 20.3), respectively; efficacy of PHiD-CV/dPly/PhtD-30 (2+1 schedule) was 0.5% (-22.1, 18.9) versus PHiD-CV. No differences were observed in pneumococcal NPC acquisition, clearance, or bacterial load. Both protein-based vaccines elicited immune responses to pneumococcal proteins.
In this high carriage prevalence setting, inclusion of pneumococcal proteins in the PHiD-CV/dPly/PhtD investigational vaccine had no impact on pneumococcal NPC in infants, regardless of protein dose or schedule. Future evaluations will assess its impact against pneumococcal disease endpoints.
PATH, GlaxoSmithKline Biologicals SA. ClinicalTrials.gov identifier NCT01262872.
保守的肺炎球菌蛋白是包含在抗肺炎球菌疾病疫苗中的潜在候选物。在一项分为两部分的研究的第一部分中，一种包含10种肺炎球菌血清型特异性多糖结合物（10VT）以及肺炎球菌溶血素类毒素和肺炎球菌组氨酸三联体蛋白D（各30μg）的研究性疫苗（PHiD-CV/dPly/PhtD-30）在冈比亚儿童中耐受性良好。本文呈现的第二部分评估了两种PHiD-CV/dPly/PhtD制剂对婴儿肺炎球菌鼻咽部携带（NPC）患病率的疗效。
在这项2期随机对照、观察者盲法试验中，从城郊卫生中心招募的8至10周龄健康婴儿被随机（1:1:1:1:1:1）分为六组。四组在2 - 3 - 4月龄（3+0婴儿免疫程序）时接受PHiD-CV/dPly/PhtD（每种蛋白10或30μg）、PHiD-CV或13价肺炎球菌结合疫苗，两组在2 - 4 - 9月龄（2+1婴儿免疫程序）时接受PHiD-CV/dPly/PhtD-30或PHiD-CV。主要目标是评估对5 - 9 - 12月龄时非10VT NPC的影响。次要目标包括对蛋白剂量优势以及安全性/反应原性的验证性分析。还探讨了对肺炎球菌NPC获得、细菌载量以及ply和phtD基因测序的影响。
2011年6月至2012年5月期间共纳入1200名婴儿。基线时肺炎球菌（60 - 67%）和非10VT（55 - 61%）NPC的患病率很高。在所有接种疫苗后的时间点，PHiD-CV/dPly/PhtD-10和PHiD-CV/dPly/PhtD-30（3+0免疫程序）对非10VT NPC的疗效分别为1.1%（95%CI -21.5, 19.5）和2.1%（-20.3, 20.3）；PHiD-CV/dPly/PhtD-30（2+1免疫程序）对非10VT NPC的疗效为0.5%（-22.1, 18.9），与PHiD-CV相比无差异。在肺炎球菌NPC获得、清除或细菌载量方面未观察到差异。两种基于蛋白的疫苗均引发了对肺炎球菌蛋白的免疫反应。
在这种携带率很高的情况下，在PHiD-CV/dPly/PhtD研究性疫苗中加入肺炎球菌蛋白对婴儿肺炎球菌NPC没有影响，无论蛋白剂量或免疫程序如何。未来的评估将评估其对肺炎球菌疾病终点的影响。
PATH、葛兰素史克生物制品公司。ClinicalTrials.gov标识符NCT01262872。
Zotero 插件