Iwata Satoshi, Kawamura Naohisa, Kuroki Haruo, Tokoeda Yasunobu, Miyazu Mitsunobu, Iwai Asayuki, Oishi Tomohiro, Sato Tomohide, Suyama Akari, François Nancy, Shafi Fakrudeen, Ruiz-Guiñazú Javier, Borys Dorota
a Department of Infectious Diseases ; School of Medicine; Keio University ; Shinjuku-ku , Tokyo , Japan.
Hum Vaccin Immunother. 2015;11(4):826-37. doi: 10.1080/21645515.2015.1012019.
This phase III, randomized, open-label, multicenter study (NCT01027845) conducted in Japan assessed the immunogenicity, safety, and reactogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, given intramuscularly) co-administered with diphtheria-tetanus-acellular pertussis vaccine (DTPa, given subcutaneously). Infants (N=360 ) were randomized (2:1) to receive either PHiD-CV and DTPa (PHiD-CV group) or DTPa alone (control group) as 3-dose primary vaccination (3-4-5 months of age) and booster vaccination (17-19 months of age). Immune responses were measured before and one month after primary/booster vaccination and adverse events (AEs) were recorded. Post-primary immune responses were non-inferior to those in pivotal/efficacy European or Latin American pneumococcal protein D-conjugate vaccine studies. For each PHiD-CV serotype, at least 92.6% of infants post-primary vaccination and at least 97.7% of children post-booster had pneumococcal antibody concentrations ≥0.2 μg/ml, and at least 95.4% post-primary and at least 98.1% post-booster had opsonophagocytic activity (OPA) titers ≥8 . Geometric mean antibody concentrations and OPA titers (except OPA titer for 6B) were higher post-booster than post-priming for each serotype. All PHiD-CV-vaccinated children had anti-protein D antibody concentrations ≥100 EL.U/ml one month post-primary/booster vaccination and all were seroprotected/seropositive against each DTPa antigen. Redness and irritability were the most common solicited AEs in both groups. Incidences of unsolicited AEs were comparable between groups. Serious AEs were reported for 47 children (28 in PHiD-CV group); none were assessed as vaccine-related. In conclusion, PHiD-CV induced robust immune responses and was well tolerated when co-administered with DTPa in a 3-dose priming plus booster regimen to Japanese children.
这项在日本开展的III期随机、开放标签、多中心研究（NCT01027845）评估了10价肺炎球菌非分型流感嗜血杆菌蛋白D结合疫苗（PHiD-CV，肌内注射）与白喉-破伤风-无细胞百日咳疫苗（DTPa，皮下注射）联合使用时的免疫原性、安全性和反应原性。360名婴儿被随机分组（2:1），分别接受PHiD-CV和DTPa联合接种（PHiD-CV组）或仅接种DTPa（对照组），作为3剂次的基础免疫（3、4、5月龄）和加强免疫（17 - 19月龄）。在基础免疫/加强免疫前及免疫后1个月测量免疫反应，并记录不良事件（AE）。基础免疫后的免疫反应不劣于关键/有效性欧洲或拉丁美洲肺炎球菌蛋白D结合疫苗研究中的反应。对于每种PHiD-CV血清型，至少92.6%的婴儿在基础免疫后以及至少97.7%的儿童在加强免疫后肺炎球菌抗体浓度≥0.2μg/ml，并且至少95.4%的婴儿在基础免疫后以及至少98.1%的儿童在加强免疫后吞噬细胞杀菌活性（OPA）滴度≥8。每种血清型加强免疫后的几何平均抗体浓度和OPA滴度（6B型的OPA滴度除外）均高于基础免疫后。所有接种PHiD-CV的儿童在基础免疫/加强免疫后1个月抗蛋白D抗体浓度≥100 EL.U/ml，并且对每种DTPa抗原均有血清保护/血清阳性反应。两组中最常见的预期AE为发红和易激惹。两组间非预期AE的发生率相当。47名儿童报告了严重AE（PHiD-CV组28名）；均未评估为与疫苗相关。总之，在日本儿童中，采用3剂次基础免疫加加强免疫方案，PHiD-CV与DTPa联合使用时诱导了强烈的免疫反应，并且耐受性良好。
