Togashi Takehiro, Mitsuya Nodoka, Kogawara Osamu, Sumino Shuji, Takanami Yohei, Sugizaki Kayoko
Hokkaido Anti-Tuberculosis Assoiciation, Kita 8, Nishi 3-28, Kita-ku, Sapporo 060-0808, Japan.
Takeda Pharmaceutical Company Limited, 1-1 Doshomachi 4-chome, Chuo-ku, Osaka 540-8645, Japan.
Vaccine. 2016 Aug 31;34(38):4635-4641. doi: 10.1016/j.vaccine.2016.05.050. Epub 2016 Jul 26.
Broad use of monovalent Haemophilus influenzae type b (Hib) conjugate vaccines based on the capsular polysaccharide polyribosyl-ribitol phosphate (PRP), has significantly reduced invasive Hib disease burden in children worldwide, particularly in children aged <1year. In Japan, PRP conjugated to tetanus toxoid (PRP-T) vaccine has been widely used since the initiation of public funding programs followed by a routine vaccination designation in 2013.
We compared the immunogenicity and safety of PRP conjugated to a non-toxic diphtheria toxin mutant (PRP-CRM197) vaccine with the PRP-T vaccine when administered subcutaneously to healthy Japanese children in a phase III study. Additionally, we evaluated the immunogenicity and safety profiles of a diphtheria-tetanus acellular pertussis (DTaP) combination vaccine when concomitantly administered with either PRP-CRM197 or PRP-T vaccines. The primary endpoint was the "long-term seroprotection rate", defined as the group proportion with anti-PRP antibody titers ⩾1.0μg/mL, after the primary series.
Long-term seroprotection rates were 99.3% in the PRP-CRM197 group and 95.6% in the PRP-T group. The intergroup difference (PRP-CRM197 group - PRP-T group) was 3.7% (95% confidence interval: 0.099-7.336), demonstrating that PRP-CRM197 vaccine was non-inferior to PRP-T vaccine (p<0.0001). Furthermore, the "short-term seroprotection rate" (anti-PRP antibody titer ⩾0.15μg/mL) before booster vaccination was higher in the PRP-CRM197 group than in PRP-T. Concomitant administration of PRP-CRM197 vaccine with DTaP vaccine showed no differences in terms of immunogenicity compared with concomitant vaccination with PRP-T vaccine and DTaP vaccine. Although CRM197 vaccine had higher local reactogenicity, overall, both Hib vaccines had acceptable safety and tolerability profiles.
The immunogenicity of PRP-CRM197 vaccine administered subcutaneously as a three-dose primary series in children followed by a booster vaccination 1year after the primary series induced protective levels of Hib antibodies with no safety or tolerability concerns.
Registered on ClinicalTrials.gov: NCT01379846.
基于荚膜多糖多聚核糖基核糖醇磷酸酯（PRP）的单价b型流感嗜血杆菌（Hib）结合疫苗的广泛使用，已显著降低了全球儿童侵袭性Hib疾病负担，尤其是1岁以下儿童。在日本，自公共资助项目启动以及2013年常规疫苗接种指定开始以来，与破伤风类毒素结合的PRP（PRP-T）疫苗已被广泛使用。
在一项III期研究中，我们比较了无毒白喉毒素突变体结合PRP（PRP-CRM197）疫苗与PRP-T疫苗皮下注射给健康日本儿童时的免疫原性和安全性。此外，我们评估了白喉-破伤风无细胞百日咳（DTaP）联合疫苗与PRP-CRM197或PRP-T疫苗同时接种时的免疫原性和安全性。主要终点是“长期血清保护率”，定义为在基础免疫系列后抗PRP抗体滴度⩾1.0μg/mL的组比例。
PRP-CRM197组的长期血清保护率为99.3%，PRP-T组为95.6%。组间差异（PRP-CRM197组 - PRP-T组）为3.7%（95%置信区间：0.099 - 7.336），表明PRP-CRM197疫苗不劣于PRP-T疫苗（p<0.0001）。此外，在加强免疫前，PRP-CRM197组的“短期血清保护率”（抗PRP抗体滴度⩾0.15μg/mL）高于PRP-T组。与PRP-T疫苗和DTaP疫苗同时接种相比，PRP-CRM197疫苗与DTaP疫苗同时接种在免疫原性方面无差异。尽管CRM197疫苗局部反应原性较高，但总体而言，两种Hib疫苗的安全性和耐受性均可接受。
在儿童中作为三剂基础免疫系列皮下注射PRP-CRM197疫苗，并在基础免疫系列后1年进行加强免疫，其诱导的Hib抗体保护水平具有免疫原性，且无安全性或耐受性问题。
在ClinicalTrials.gov注册：NCT01379846。
