Vi-DT 结合疫苗在 6 - 23 月龄儿童中的安全性和免疫原性：II 期随机、剂量方案、观察者盲法研究。
Safety and immunogenicity of Vi-DT conjugate vaccine among 6-23-month-old children: Phase II, randomized, dose-scheduling, observer-blind Study.
作者信息
Capeding Maria Rosario, Sil Arijit, Tadesse Birkneh Tilahun, Saluja Tarun, Teshome Samuel, Alberto Edison, Kim Deok Ryun, Park Eun Lyeong, Park Ju Yeon, Yang Jae Seung, Chinaworapong Suchada, Park Jiwook, Jo Sue-Kyoung, Chon Yun, Yang Seon-Young, Ryu Ji Hwa, Cheong Inho, Shim Kyu-Young, Lee Yoonyeong, Kim Hun, Lynch Julia A, Kim Jerome H, Excler Jean-Louis, Wartel T Anh, Sahastrabuddhe Sushant
机构信息
Research Institute for Tropical Medicine, Manila, The Philippines.
International Vaccine Institute, Seoul, Republic of Korea.
出版信息
EClinicalMedicine. 2020 Sep 9;27:100540. doi: 10.1016/j.eclinm.2020.100540. eCollection 2020 Oct.
BACKGROUND
Typhoid causes significant mortality among young children in resource-limited settings. Conjugate typhoid vaccines could significantly reduce typhoid-related child deaths, but only one WHO-prequalified typhoid conjugate vaccine exists for young children. To address this gap, we investigated the safety, immunogenicity and dose-scheduling of Vi-DT typhoid conjugate vaccine among children aged 6-23 months.
METHODS
In this single center, observer blind, phase II trial, participants were randomly assigned (2:2:1) to receive one or two doses of Vi-DT or comparator vaccine. Anti-Vi IgG titer and geometric mean titers (GMT) were determined at 0, 4, 24 and 28 weeks. Data were analyzed using per-protocol and immunogenicity (a subset of intention-to-treat analysis) sets. The trial is registered with ClinicalTrials.gov (NCT03527355).
FINDINGS
Between April and July 2018, 285 children were randomized; 114 received one or two doses of Vi-DT while 57 received comparator. 277 completed the study follow-up per protocol; 112 and 110 from single- and two-dose Vi-DT schedules, respectively and 55 from the placebo group were included in the per protocol analysis. Safety profile is satisfactory. Thirteen serious adverse events were reported during the 28-week follow-up, none of which were related to Vi-DT. The seroconversion rate four weeks after the first dose was 100% (95% CI 98·3-100) in Vi-DT recipients and 7·0% (95% CI 2·8-16·7) in comparator recipients (p<0·0001). Similarly, the seroconversion rate 4 weeks after the second dose was 98·2% (95% CI 93· 6-99·5) and 21·8% (95% CI 13·0-34·4) among Vi-DT and comparator groups, respectively (p<0·0001). Anti-Vi IgG GMT was significantly higher in Vi-DT than in control group at all post-vaccination visits (p<0·0001).
INTERPRETATION
Both single and two doses of Vi-DT vaccine are safe, well tolerated, and immunogenic for infants and toddlers in a moderately endemic setting.
背景
在资源有限的环境中，伤寒在幼儿中导致相当高的死亡率。结合型伤寒疫苗可显著降低与伤寒相关的儿童死亡，但世卫组织预认证的适用于幼儿的伤寒结合疫苗只有一种。为填补这一空白，我们调查了Vi-DT伤寒结合疫苗在6至23个月大儿童中的安全性、免疫原性和剂量方案。
方法
在这项单中心、观察者盲法的II期试验中，参与者被随机分配（2:2:1）接受一剂或两剂Vi-DT或对照疫苗。在第0、4、24和28周测定抗Vi IgG滴度和几何平均滴度（GMT）。使用符合方案集和免疫原性集（意向性分析的一个子集）进行数据分析。该试验已在ClinicalTrials.gov注册（NCT03527355）。
结果
2018年4月至7月，285名儿童被随机分组；114名接受一剂或两剂Vi-DT，57名接受对照疫苗。277名按方案完成了研究随访；符合方案分析纳入了分别来自单剂量和两剂量Vi-DT方案的112名和110名儿童以及安慰剂组的55名儿童。安全性良好。在28周的随访期间报告了13起严重不良事件，均与Vi-DT无关。Vi-DT接种者在第一剂后四周的血清转化率为100%（95%CI 98·3-100），对照疫苗接种者为7·0%（95%CI 2·8-16·7）（p<0·0001）。同样，第二剂后4周，Vi-DT组和对照疫苗组的血清转化率分别为98·2%（95%CI 93·6-99·5）和21·8%（95%CI 13·0-34·4）（p<0·0001）。在所有疫苗接种后的访视中，Vi-DT组的抗Vi IgG GMT显著高于对照组（p<0·0001）。
解读
在中度流行环境中，单剂量和两剂量Vi-DT疫苗对婴幼儿均安全、耐受性良好且具有免疫原性。
Zotero 插件