Lalwani Sanjay, Chatterjee Sukanta, Chhatwal Jugesh, Simon Anna, Ravula Sudheer, Francois Nancy, Mehta Shailesh, Strezova Ana, Borys Dorota
Department of Pediatrics, Bharati Vidyapeeth Deemed University Medical College, Pune, India
KPC Medical College, Kolkata, India.
Clin Vaccine Immunol. 2014 Sep;21(9):1292-300. doi: 10.1128/CVI.00068-14. Epub 2014 Jul 9.
In this phase III, open-label, multicenter, and descriptive study in India, children primed with 3 doses (at ages 6, 10, and 14 weeks) of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were randomized (1:1) to receive a booster dose at 9 to 12 (early booster) or 15 to 18 months old (late booster) in order to evaluate impact of age at booster. We also evaluated a 2-dose catch-up vaccination plus an experimental booster dose in unprimed children age 12 to 18 months. The early booster, late booster, and catch-up vaccinations were administered to 74, 95, and 87 children, respectively; 66, 71, and 81 children, respectively, were included in the immunogenicity according-to-protocol cohort. One month postbooster, for each PHiD-CV serotype, ≥95.2% (early booster) and ≥93.8% (late booster) of the children had antibody concentrations of ≥0.2 μg/ml; ≥96.7% and ≥93.0%, respectively, had opsonophagocytic activity (OPA) titers of ≥8. The postbooster antibody geometric mean concentrations (GMCs) were in similar ranges for early and late boosters; the OPA titers appeared to be lower for most PHiD-CV serotypes (except 6B and 19F) after the early booster. After dose 2 and postbooster, for each PHiD-CV serotype, ≥88.6% and ≥96.3%, respectively, of the catch-up immunogenicity according-to-protocol cohort had antibody concentrations of ≥0.2 μg/ml; ≥71.4% and ≥90.6%, respectively, had OPA titers of ≥8. At least 1 serious adverse event was reported by 2 children in the early booster (skin infection and gastroenteritis) and 1 child in the catch-up group (febrile convulsion and urinary tract infection); all were resolved, and none were considered by the investigators to be vaccine related. PHiD-CV induced robust immune responses regardless of age at booster. Booster vaccination following 2 catch-up doses induced robust immune responses indicative of effective priming and immunological memory. (These studies have been registered at www.clinicaltrials.gov under registration no. NCT01030822 and NCT00814710; a protocol summary is available at www.gsk-clinicalstudyregister.com [study ID 112909]).
在印度进行的这项III期、开放标签、多中心描述性研究中，接受过3剂（6周、10周和14周龄）10价肺炎球菌非分型流感嗜血杆菌蛋白D结合疫苗（PHiD-CV）基础免疫的儿童被随机分组（1:1），在9至12个月龄（早期加强免疫）或15至18个月龄（晚期加强免疫）接受一剂加强免疫，以评估加强免疫年龄的影响。我们还评估了在12至18个月龄未接受基础免疫的儿童中进行2剂补种疫苗加一剂试验性加强免疫的情况。早期加强免疫、晚期加强免疫和补种疫苗分别接种了74名、95名和87名儿童；分别有66名、71名和81名儿童被纳入符合方案的免疫原性队列。加强免疫后1个月，对于每种PHiD-CV血清型，≥95.2%（早期加强免疫）和≥93.8%（晚期加强免疫）的儿童抗体浓度≥0.2μg/ml；分别有≥96.7%和≥93.0%的儿童吞噬细胞杀菌活性（OPA）滴度≥8。早期和晚期加强免疫后加强免疫的抗体几何平均浓度（GMC）处于相似范围；早期加强免疫后，大多数PHiD-CV血清型（6B和19F除外）的OPA滴度似乎较低。在第2剂疫苗接种后和加强免疫后，对于每种PHiD-CV血清型，符合方案的补种免疫原性队列中分别有≥88.6%和≥96.3%的儿童抗体浓度≥0.2μg/ml；分别有≥71.4%和≥90.6%的儿童OPA滴度≥8。早期加强免疫组有2名儿童（皮肤感染和肠胃炎）和补种组有1名儿童（热性惊厥和尿路感染）报告了至少1起严重不良事件；所有事件均已解决，研究人员认为均与疫苗无关。无论加强免疫的年龄如何，PHiD-CV均能诱导强烈的免疫反应。2剂补种疫苗后进行加强免疫可诱导强烈的免疫反应，表明基础免疫有效且存在免疫记忆。（这些研究已在www.clinicaltrials.gov上注册，注册号为NCT01030822和NCT00814710；方案摘要可在www.gsk-clinicalstudyregister.com[研究ID 112909]上获取。）
