Discussion
typhoid conjugate vaccine, typhoid
ADVERSE EVENTS, MINOR, SUBCLINICAL INFECTION, TYPHOID
This study shows that a single dose of Vi-DT vaccine is safe and immunologically non-inferior to the comparator Vi-TT vaccine at 4 weeks postvaccination in the studied age groups.We found no significant difference in anti-Vi IgG seroconversion rates between Vi-DT vaccine (groups A-C) and Vi-TT vaccine (group D) at 4 weeks (100.00% vs 98.99%) and 24 weeks (98.98% vs 97.87%). Immune non-inferiority of Vi-DT vaccine compared with Vi-TT vaccine at 4 weeks postvaccination was proven with the lower limit of 97.5% CI of difference between the seroconversion proportions being −3.07%, which was greater than the predefined non-inferiority margin of −10%. The proportions of participants reporting adverse events after vaccination were comparable in Vi-DT and Vi-TT groups with no significant difference.There are various types of typhoid conjugate vaccines being studied in different population and are at various stages of development.The results from the present study demonstrating non-inferior immunogenicity and safety of single dose Vi-DT vaccine versus the licensed WHO prequalified Vi-TT vaccine with comparable results in various age strata add further evidence to support its licensure and WHO prequalification, and thereby, add to the current supply chain and diversity of TCV portfolio to meet global demands.Our study was affected by the ongoing COVID-19 pandemic. One of the limitations was the follow-up visits being affected by the respective travel restrictions, causing many predefined visits to not be conducted within the visit window, which in turn increased the number of protocol deviations. However, these protocol deviations had minor effects on the per-protocol analyses. Lot to lot consistency of the different lots of Vi-DT vaccine could not be commented upon from this sub-study and has been demonstrated in the main study. (2) In this study, we could not study the immune noninterference of Vi-DT typhoid conjugate vaccine with measles-rubella vaccine due to unavailability of sufficient number of eligible participants during the study period. Additionally, as Nepal is a typhoid-endemic country, there was a possibility of enrolling individuals with subclinical infection or individuals who were asymptomatic carriers of typhoid affecting this study. However, there would have been equal distribution of any potential sources of error among the 4 randomized groups, thus not affecting the statistical comparisons.In conclusion, our study shows that a single dose of Vi-DT test vaccine has seroconversion rates similar to Vi-TT Typbar TCV