Safety and immunogenicity of Vi-DT conjugate vaccine among 6-23-month-old children: Phase II, randomized, dose-scheduling, observer-blind Study

• Main Authors: Maria Rosario Capeding, Arijit Sil, Birkneh Tilahun Tadesse, Tarun Saluja, Samuel Teshome, Edison Alberto, Deok Ryun Kim, Eun Lyeong Park, Ju Yeon Park, Jae Seung Yang, Suchada Chinaworapong, Jiwook Park, Sue-Kyoung Jo, Yun Chon, Seon-Young Yang, Ji Hwa Ryu, Inho Cheong, Kyu-Young Shim, Yoonyeong Lee, Hun Kim, Julia A. Lynch, Jerome H. Kim, Jean-Louis Excler, T. Anh Wartel, Sushant Sahastrabuddhe
• Format: Article
• Language: English
• Published: Elsevier 2020-10-01
• Series: EClinicalMedicine
• Subjects: Infants and toddlers; Typhoid; typhoid conjugate vaccine; Vi-DT
• Online Access: http://www.sciencedirect.com/science/article/pii/S2589537020302844

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.