Persistence of immune responses 5 years after vaccination with a single dose of typhoid conjugate vaccine (TCV) in Nepalese children

Background: A single-dose typhoid conjugate vaccine (TCV) has been recommended in endemic settings. Here we report the 5-year immunogenicity results post a single dose of TCV in Nepal. Methods: We conducted a participant and observer-blinded randomised trial (RCT) in Lalitpur, Nepal (2017-2021). 20,019 children aged 9 months to ≤16 years were randomised to receive Vi-TT or MenA. After unblinding in 2020-2021, children were offered the alternate vaccine and were followed till 2025. A subgroup of 1500 participants (1000 Vi-TT, 500 MenA) were recruited into the immunogenicity cohort, who had blood samples taken at day 0, day 28, 18 months, 2,4, and 5 years post-baseline. The primary outcome is anti-Vi antibody responses. Results: The median age at TCV vaccination was 10.1 in the 2017/2018 cohort and 13.1 in the 2020/2021 cohort. The geometric mean concentration (GMC) anti-Vi IgG was2037.90 (95% CI: 1904.86-2180.23) at day 28, dropping to 241.29 (220.27-264.31) at 18 months. At 5 years post vaccination, the GMCwas109.3 (98.65-121.10). The sero-conversion rates at 5 years post-vaccination remained high (88%). Antibody decay was significantly slower in older children, females, and children with detectable baseline anti-Vi IgG, compared with their respective reference groups. Anti-Vi IgA was highly correlated with IgG (p<0.0001). Interpretation: This study provides evidence that anti-Vi immunity is sustained for at least 5 years post-vaccination. Children vaccinated at younger ages showed a faster decline, highlighting the need for further investigation into the optimal age for vaccination and the need for boosters.