University Hospital, Hradec Kralove, Czech Republic.
University Hospital, Pilsen, Czech Republic.
Vaccine. 2014 May 23;32(25):3025-34. doi: 10.1016/j.vaccine.2014.03.066. Epub 2014 Apr 1.
To provide broader protection against pneumococcal disease, new vaccines containing conserved Streptococcus pneumoniae proteins are being developed. This study assessed the safety, reactogenicity and immunogenicity of four formulations containing pneumococcal proteins pneumolysin toxoid (dPly) and histidine triad protein (PhtD) in toddlers.
In this phase II, multicenter, observer-blind study (www.clinicaltrials.gov: NCT00985751) conducted in the Czech Republic, toddlers (12-23 months) were randomized (1:1:1:1:1) to receive one of four investigational vaccine formulations (10 or 30μg each of dPly and PhtD, alone or in combination with polysaccharide conjugates from the pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine [PHiD-CV]), or the licensed PHiD-CV, in a 2-dose primary series plus booster at study months 0, 2 and 6. Solicited local and general symptoms were recorded within seven days post-vaccination, unsolicited symptoms within 31 days post-vaccination, and serious adverse events (SAEs) during the entire study period. Antibody concentrations against the vaccine components were measured pre-vaccination, one month post-dose 2, pre- and one month post-booster.
257 toddlers were enrolled and vaccinated. Percentages of solicited local and general symptoms following the different investigational formulations were generally within the same ranges as for PHiD-CV. After each dose, grade 3 fever (>40.0°C, rectal measurement) was reported for maximum one toddler in each group with no differences between investigational formulations and PHiD-CV during primary vaccination. 23 SAEs were reported for 17 toddlers, with distribution balanced between all groups except the group receiving 30 μg dPly/PhtD with PHiD-CV-conjugates (no SAEs reported). None of the SAEs were considered to be vaccine-related. For all pneumococcal protein-containing formulations, anti-PhtD and anti-Ply antibody geometric mean concentrations increased from pre-vaccination to post-dose 2 and from pre- to post-booster vaccination.
All investigational vaccine formulations were well-tolerated and immunogenic when administered to toddlers as a 2-dose primary vaccination followed by a booster dose.
为了提供更广泛的肺炎球菌疾病保护，正在开发含有保守肺炎链球菌蛋白的新疫苗。本研究评估了四种含有肺炎球菌蛋白肺炎球菌溶素毒素（dPly）和组氨酸三联体蛋白（PhtD）的制剂在幼儿中的安全性、反应原性和免疫原性。
这是一项在捷克共和国进行的、多中心、观察者盲法的 II 期研究（www.clinicaltrials.gov：NCT00985751）。12-23 个月大的幼儿被随机（1:1:1:1:1）分为四组，分别接受四种研究性疫苗制剂（dPly 和 PhtD 各 10 或 30μg，单独或与无型流感嗜血杆菌蛋白-D 结合疫苗 [PHiD-CV] 的多糖结合物联合使用）之一，或接受已上市的 PHiD-CV，在 0、2 和 6 个月时进行两剂初级系列加加强剂。接种后 7 天内记录疫苗接种后局部和全身症状，接种后 31 天内记录未报告症状，整个研究期间记录严重不良事件（SAE）。在接种前、第二剂接种后 1 个月、接种前和加强针接种后 1 个月测量针对疫苗成分的抗体浓度。
共纳入 257 名幼儿并进行了接种。不同研究性制剂接种后的局部和全身症状百分比通常与 PHiD-CV 相似。每次接种后，每组均有一名幼儿报告最高 3 级发热（直肠测量 >40.0°C），在初级接种期间，研究性制剂与 PHiD-CV 之间无差异。17 名幼儿报告了 23 例 SAE，分布在所有组之间平衡，除了接受 30μg dPly/PhtD 与 PHiD-CV 结合物的组（无 SAE 报告）。没有一个 SAE 被认为与疫苗有关。对于所有含有肺炎球菌蛋白的制剂，接种后 2 剂和接种前至加强针接种后，抗 PhtD 和抗 Ply 抗体几何平均浓度均从接种前增加。
当作为两剂初级疫苗接种后再进行一剂加强针接种时，所有研究性疫苗制剂在幼儿中均具有良好的耐受性和免疫原性。
