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

Abstract

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.

Safety and immunogenicity of the Vi-DT typhoid conjugate vaccine in healthy volunteers in Nepal: an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial

“…The Vi-DT vaccine safety and reactogenicity data are consistent with those reported in other phase 3 studies of the Vi-TT vaccine, and they confirm the safety profile of the phase 2 study of the Vi-DT vaccine in children younger than 2 years. 11,13,17 Overall, our study shows that the Vi-DT test vaccine is safe, immunogenic, and non-inferior to the licensed Vi-TT vaccine when given as a single dose in all age groups, including in children aged 6 months to younger than 2 years. The Vi-DT vaccine was non-inferior to the Vi-TT vaccine in all participants and in each age stratum in terms of the anti-Vi IgG seroconversion rate, and the Vi-DT vaccine lot-to-lot consistency, measured by anti-Vi IgG GMTs, was shown at 4 weeks following vaccination.…”

Evaluation of Typhoid Conjugate Vaccine Effectiveness in Ghana (TyVEGHA) Using a Cluster-Randomized Controlled Phase IV Trial: Trial Design and Population Baseline Characteristics

“…Additionally, two programs evaluating Vi-DT (Vi-polysaccharide-conjugated diphtheria toxoid) conjugate approaches (SK Bioscience, Seongnam, Korea and PT BioFarma, Bandung, Indonesia) are in late-stage clinical development and are expected to receive WHO prequalification by 2022. Vi-DT was shown to elicit strong immune responses and has a very strong safety profile [ 16 , 17 , 33 ]. There is ongoing discussion within the THECA consortium to use one of these newly prequalified TCV candidates in a mass vaccination campaign followed by a prospective cohort study to estimate real-life effectiveness in other African countries.…”

“…Overall, TCVs have been shown to have a reassuringly safety profile across age groups including infants and children [ 13 , 14 , 15 , 16 , 17 ]. An individually randomized trial of Vi-TT in Nepal, conducted by the Typhoid Vaccine Acceleration Consortium (TyVAC) led by the University of Maryland in partnership with the University of Oxford and PATH, determined the vaccine efficacy to be 81.6% (95% confidence interval, between 58.8% and 91.8%), while another trial in Malawi is expected to provide estimates of efficacy within this year [ 18 , 19 ].…”

Supply and delivery of vaccines for global health

“…Initially transferred to Shantha Biotechnics, the technology was transferred to SK bioscience (Republic of Korea), PT Bio Farma (Indonesia), and Incepta Vaccines (Bangladesh) [ 38 • ]. After promising Phase II results [ 39 ], SK bioscience Vi-DT has completed Phase 3 in Nepal and the Philippines, and plans for WHO PQ.…”