Klein Nicola P, Abu-Elyazeed Remon, Cornish Matthew, Leonardi Michael L, Weiner Leonard B, Silas Peter E, Grogg Stanley E, Varman Meera, Frenck Robert W, Cheuvart Brigitte, Baine Yaela, Miller Jacqueline M, Leyssen Maarten, Mesaros Narcisa, Roy-Ghanta Sumita
Kaiser Permanente Vaccine Study Center, 1 Kaiser Plaza, 16th Floor, Oakland, CA 94612, United States.
GSK, 5 Crescent Drive, Philadelphia, PA 19112, United States.
Vaccine. 2017 Jun 16;35(28):3564-3574. doi: 10.1016/j.vaccine.2017.05.018. Epub 2017 May 20.
Vaccination against Haemophilus influenzae type b (Hib) is included in routine pediatric immunization schedule in the United States. Previous vaccine shortages have created the need for additional options for Hib vaccination.
This phase III, randomized, multi-centered study (NCT01000974) evaluated the safety and immunogenicity of a monovalent tetanus toxoid-conjugate Hib vaccine (Hib-TT) compared to a monovalent (Hib-TT control) and a combination Hib-TT vaccine. We hierarchically assessed lot-to-lot consistency of 3 Hib-TT lots and non-inferiority of Hib-TT to Hib-TT control. We co-administered routine pediatric vaccines with Hib-TT vaccines at 2, 4, 6months (primary vaccination) and 15-18months of age (booster vaccination). We recorded adverse events (AEs) for 4 (solicited) and 31days (unsolicited) post-vaccination and serious AEs (SAEs) throughout the study.
Of 4009 enrolled children, 3086 completed booster phase. Lot-to-lot consistency was not demonstrated. The study met statistical criteria for non-inferiority of Hib-TT to Hib-TT control in terms of immune responses to Hib and co-administered vaccines' antigens, but not in terms of participants achieving post-primary vaccination anti-PRP levels ≥1µg/mL. Because of the hierarchical nature of the objectives, non-inferiority could not be established. In all groups, 92.5-96.7% and 99.6-100% of participants achieved anti-PRP levels ≥0.15µg/mL, while 78.3-89.8% and 97.9-99.1% had anti-PRP levels ≥1µg/mL, post-primary and post-booster vaccination, respectively. Immune responses to co-administered vaccines and reported incidence of AEs were comparable among groups. We recorded SAEs for 107/2963 (3.6%), 24/520 (4.6%), and 21/520 (4.0%) children post-primary vaccination, and 29/2337 (1.2%), 4/435 (0.9%), and 2/400 (0.5%) children post-booster vaccination with Hib-TT, Hib-TT control and combination Hib-TT vaccine, respectively; 6/5330 (0.1%) SAEs in the Hib-TT groups were considered vaccine-related.
Hib-TT induced seroprotective antibody concentrations in the majority of participants and was well-tolerated when co-administered with routine pediatric vaccines according to a 3+1 schedule.
在美国，b型流感嗜血杆菌（Hib）疫苗接种已纳入常规儿童免疫计划。以往的疫苗短缺使得需要有更多的Hib疫苗接种选择。
这项III期随机多中心研究（NCT01000974）评估了单价破伤风类毒素结合Hib疫苗（Hib-TT）与单价（Hib-TT对照）及联合Hib-TT疫苗相比的安全性和免疫原性。我们分层评估了3批Hib-TT的批间一致性以及Hib-TT相对于Hib-TT对照的非劣效性。我们在2、4、6月龄（基础免疫）和15 - 18月龄（加强免疫）时将常规儿童疫苗与Hib-TT疫苗同时接种。我们记录了接种疫苗后4天（预期的）和31天（非预期的）的不良事件（AE）以及整个研究期间的严重不良事件（SAE）。
在4009名入组儿童中，3086名完成了加强免疫阶段。未证明批间一致性。该研究在Hib免疫反应及同时接种疫苗的抗原方面达到了Hib-TT相对于Hib-TT对照非劣效性的统计标准，但在基础免疫后参与者抗PRP水平≥1μg/mL方面未达到。由于目标的分层性质，无法确定非劣效性。在所有组中，基础免疫和加强免疫后分别有92.5 - 96.7%和99.6 - 100% 的参与者抗PRP水平≥0.15μg/mL，而抗PRP水平≥1μg/mL的分别为78.3 - 89.8%和97.9 - 99.1%。各小组间对同时接种疫苗的免疫反应及报告的AE发生率相当。我们记录到基础免疫后，分别有107/2963（3.6%）、24/520（4.6%）和21/520（4.0%）的儿童发生SAE，加强免疫后，接种Hib-TT、Hib-TT对照和联合Hib-TT疫苗的儿童中发生SAE的分别为29/2337（1.2%）、4/435（0.9%）和2/400（0.5%）；Hib-TT组中6/5330（0.1%）的SAE被认为与疫苗相关。
Hib-TT在大多数参与者中诱导产生了血清保护性抗体浓度，并且按照3 + 1程序与常规儿童疫苗同时接种时耐受性良好。
