Vesikari Timo, Rivera Luis, Korhonen Tiina, Ahonen Anitta, Cheuvart Brigitte, Hezareh Marjan, Janssens Winnie, Mesaros Narcisa
a Vaccine Research Center , University of Tampere , Tampere , Finland.
b Hospital Maternidad Nuestra Señora de la Altagracia Santo Domingo , Santo Domingo , Dominican Republic.
Hum Vaccin Immunother. 2017 Jul 3;13(7):1505-1515. doi: 10.1080/21645515.2017.1294294. Epub 2017 Mar 24.
Safety and immunogenicity of 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens of the combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis-Hib vaccine (DTPa-HBV-IPV/Hib) were evaluated in a Primary (NCT01248884) and a Booster vaccination (NCT01453998) study. In the Primary study, 721 healthy infants (randomized 1:1:1) received 3 doses of DTPa-HBV-IPV/Hib formulation A (DTPa-HBV-IPV/Hib), or B (DTPa-HBV-IPV/Hib) or the licensed DTPa-HBV-IPV/Hib vaccine (Infanrix hexa, GSK; control group) at 2, 3, 4 months of age. Infants were planned to receive a booster dose at 12-15 months of age with the same formulation received in the Primary study; however, following high incidence of fever associated with the investigational formulations in the Primary study, the Booster study protocol was amended and all infants yet to receive a booster dose (N = 385) received the licensed vaccine. In the Primary study, non-inferiority of 3-dose vaccination with investigational formulations compared with the licensed vaccine was not demonstrated due to anti-pertactin failing to meet the non-inferiority criterion. Post-primary vaccination, most infants had seroprotective levels of anti-diphtheria (100% of infants), anti-tetanus antigens (100%), against hepatitis B (≥ 97.5% across groups), polyribosyl-ribitol-phosphate (≥ 88.0%) and poliovirus types 1-3 (≥ 90.5%). Seropositivity rates for each pertussis antigen were 100% in all groups. Higher incidence of fever (> 38°C) was reported in infants receiving the investigational formulations (Primary study: 75.0% [A] and 72.1% [B] vs 58.8% [control]; Booster study, before amendment: 49.4% and 46.6% vs 37.4%, respectively). The development of the investigational formulations was not further pursued.
在一项初次免疫（NCT01248884）和一项加强免疫（NCT01453998）研究中，对联合白喉-破伤风-无细胞百日咳-乙型肝炎-灭活脊髓灰质炎- b型流感嗜血杆菌疫苗（DTPa-HBV-IPV/Hib）的2种白喉、破伤风和b型流感嗜血杆菌抗原研究制剂的安全性和免疫原性进行了评估。在初次免疫研究中，721名健康婴儿（随机分为1:1:1）在2、3、4月龄时接受3剂DTPa-HBV-IPV/Hib制剂A（DTPa-HBV-IPV/Hib）、制剂B（DTPa-HBV-IPV/Hib）或已获许可的DTPa-HBV-IPV/Hib疫苗（Infanrix hexa，葛兰素史克公司；对照组）。计划婴儿在12至15月龄时接受与初次免疫研究中相同制剂的加强剂量；然而，由于初次免疫研究中研究制剂相关发热的高发生率，加强免疫研究方案进行了修订，所有尚未接受加强剂量的婴儿（N = 385）均接受了已获许可的疫苗。在初次免疫研究中，由于抗百日咳杆菌黏附素未达到非劣效性标准，未证明研究制剂3剂接种与已获许可疫苗相比具有非劣效性。初次免疫接种后，大多数婴儿的抗白喉（100%的婴儿）、抗破伤风抗原（100%）、抗乙型肝炎（各组≥97.5%）、多聚核糖基核糖醇磷酸（≥88.0%）和1-3型脊髓灰质炎病毒（≥90.5%）的血清保护水平达标。所有组中每种百日咳抗原的血清阳性率均为100%。接受研究制剂的婴儿中报告的发热（>38°C）发生率较高（初次免疫研究：75.0%[A组]和72.1%[B组] vs 58.8%[对照组]；加强免疫研究，修订前：分别为49.4%和46.6% vs 37.4%）。未进一步推进研究制剂的研发。
