Miyazu Mitsunobu, Kikuchi Hitoshi, Hamada Atsuo, Fukushima Shinji, Ouchi Kazunobu, Bosch Castells Valerie, Mihara Hanako, Bonnet Marie-Claude
Meitetsu Hospital, Sako, Nishi-ku, Nagoya-Shi, Aichi, Japan.
Tokyo Medical University Hospital, Nishi-Shinjuku, Shinjuku-Ku, Tokyo, Japan.
Vaccine. 2015 Nov 27;33(48):6697-702. doi: 10.1016/j.vaccine.2015.10.086. Epub 2015 Oct 28.
Although typhoid fever is rare in Japan, imported cases have been reported occasionally in travelers returning from endemic areas. To achieve licensing of a typhoid Vi polysaccharide vaccine (Typhim Vi(®)) and make it widely available in Japan, this study was conducted at the request of the Japanese Ministry of Health Labor and Welfare to assess the immunogenicity and safety of this vaccine when given as a single dose (the recommended schedule of administration) in a Japanese population.
In this multi-center, open-label, non-comparative, intervention study performed in Japan, 200 healthy volunteers (188 adults [≥ 18 years of age], 7 adolescents [12-17 years of age] and 5 children [2-11 years of age]) were administered Typhim Vi(®). Immunogenicity was assessed 28 days after vaccinations using an ELISA method of anti-Vi antibody detection. A 4-fold increase in anti-Vi titer was considered as the threshold for seroconversion for anti-Vi antibodies. Safety was assessed up to 28 days following vaccination.
Overall, 92.0% (95% confidence interval [CI]: 87.3-95.4%) of participants achieved seroconversion 28 days after a single dose of typhoid Vi polysaccharide vaccine. GMTs of Vi antibody titers increased from 6.6 (95% CI: 5.8-7.4) prior to vaccination to 157.3 (95% CI: 135.1-183.2) on Day 28 after vaccination. The geometric mean of individual anti-Vi antibody titer ratios (Day 28/Day 0) was 23.9 (95% CI: 20.3-28.3). There were no immediate adverse events and no adverse events led to the discontinuation of participants from the study. Across all age groups, pain and myalgia were the most frequently reported injection site and systemic reactions, respectively. Most of these reactions were mild in intensity and resolved within 7 days.
A single dose of typhoid Vi polysaccharide vaccine, Typhim Vi(®), demonstrated good safety and immunogenicity profile in a Japanese population.
尽管伤寒热在日本较为罕见，但偶尔会有从流行地区返回的旅行者出现输入性病例的报告。为使伤寒Vi多糖疫苗（Typhim Vi®）获得许可并在日本广泛供应，本研究应日本厚生劳动省的要求开展，旨在评估该疫苗在日本人群中作为单剂量（推荐给药方案）使用时的免疫原性和安全性。
在日本进行的这项多中心、开放标签、非对照干预研究中，200名健康志愿者（188名成年人[≥18岁]、7名青少年[12 - 17岁]和5名儿童[2 - 11岁]）接种了Typhim Vi®。接种疫苗28天后，采用ELISA法检测抗Vi抗体来评估免疫原性。抗Vi滴度增加4倍被视为抗Vi抗体血清转化的阈值。接种疫苗后长达28天评估安全性。
总体而言，单剂量伤寒Vi多糖疫苗接种28天后，92.0%（95%置信区间[CI]：87.3 - 95.4%）的参与者实现了血清转化。接种疫苗前Vi抗体滴度的几何平均浓度（GMT）为6.6（95% CI：5.8 - 7.4），接种后第28天升至157.3（95% CI：135.1 - 183.2）。个体抗Vi抗体滴度比值（第28天/第0天）的几何平均值为23.9（95% CI：20.3 - 28.3）。未出现即刻不良事件，也没有不良事件导致参与者退出研究。在所有年龄组中，疼痛和肌痛分别是最常报告的注射部位反应和全身反应。这些反应大多强度较轻，7天内缓解。
单剂量伤寒Vi多糖疫苗Typhim Vi®在日本人群中显示出良好的安全性和免疫原性。
