Research Institute for Tropical Medicine, Manila, Philippines.
International Vaccine Institute, Seoul, Republic of Korea.
Vaccine. 2018 Jun 18;36(26):3794-3801. doi: 10.1016/j.vaccine.2018.05.038.
Typhoid fever remains a major public health problem in low- and middle-income countries where children aged 2-14 years bear the greatest burden. Vi polysaccharide is poorly immunogenic in children <2 years of age, and protection in adults is modest. The limitations of Vi polysaccharide vaccines can be overcome by conjugation of the Vi to a carrier protein. A typhoid conjugate vaccine composed of Vi polysaccharide conjugated to diphtheria toxoid (Vi-DT) has been developed. The Phase I study results are presented here.
This was a randomized, observer-blinded Phase I study to assess the safety and immunogenicity of Vi-DT compared to Vi polysaccharide vaccine, conducted in Manila, Philippines. Participants enrolled in an age de-escalation manner (18-45, 6-17 and 2-5 years) were randomized between Test (Vi-DT, 25 µg) administered at 0 and 4 weeks and Comparator (Vi polysaccharide, Typhim Vi® and Vaxigrip®, Sanofi Pasteur) vaccines.
A total of 144 participants were enrolled (48 by age strata, 24 in Test and Comparator groups each). No serious adverse event was reported in either group. Solicited and unsolicited adverse events were mild or moderate in both groups with the exception of a 4-year old girl in Test group with grade 3 fever which resolved without sequelae. All participants in Test group seroconverted after first and second doses of Vi-DT while the proportions in the Comparator group were 97.1% and 97.2%, after first dose of Typhim Vi® and second dose of Vaxigrip®, respectively. Vi-DT showed 4-fold higher Geometric Mean Titers (GMT) compared to Typhim Vi® (adjusted for age strata, p < 0.001). No further increase of GMT was detected after the second dose of Vi-DT. Anti-DT IgG seroresponse rates were 81.2% and 84.5% post first and second Vi-DT doses, respectively.
Vi-DT vaccine was safe, well-tolerated and immunogenic in participants aged 2-45 years. ClinicalTrials.gov registration number: NCT02645032.
伤寒在中低收入国家仍然是一个主要的公共卫生问题，其中 2-14 岁的儿童负担最大。Vi 多糖在 2 岁以下儿童中的免疫原性较差，而成人保护作用有限。通过将 Vi 与载体蛋白偶联，可以克服 Vi 多糖疫苗的局限性。一种由 Vi 多糖与白喉类毒素偶联而成的伤寒结合疫苗（Vi-DT）已经被开发出来。本文报告了其 I 期研究结果。
这是一项在菲律宾马尼拉进行的随机、观察者盲法 I 期研究，旨在评估 Vi-DT 与 Vi 多糖疫苗相比的安全性和免疫原性。参与者按年龄递减方式（18-45、6-17 和 2-5 岁）入组，并随机分为试验组（Vi-DT，25μg）和对照组（Vi 多糖疫苗，Typhim Vi®和 Vaxigrip®，赛诺菲巴斯德），分别在 0 周和 4 周时进行接种。
共纳入 144 名参与者（按年龄分层，每组 48 人；试验组和对照组各 24 人）。两组均未报告严重不良事件。两组的不良事件均为轻度或中度，仅一名试验组的 4 岁女孩出现 3 级发热，但无后遗症。所有试验组参与者在接种第一和第二剂 Vi-DT 后均发生血清转换，而对照组参与者在接种第一剂 Typhim Vi®和第二剂 Vaxigrip®后，血清转换比例分别为 97.1%和 97.2%。与 Typhim Vi®相比，Vi-DT 的几何平均滴度（GMT）高出 4 倍（按年龄分层调整，p<0.001）。接种第二剂 Vi-DT 后，GMT 无进一步升高。接种第一和第二剂 Vi-DT 后，抗-DT IgG 血清应答率分别为 81.2%和 84.5%。
Vi-DT 疫苗在 2-45 岁的参与者中安全、耐受且具有免疫原性。临床试验注册编号：NCT02645032。
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