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) (ISRCTN43385161). 20,019 children aged 9 months to ≤16 years were randomised to receive Typbar TCV (Vi-TT; Bharat Biotech International, India) or capsular group A meningococcal conjugate vaccine (MenA) in 2017-2018. After unblinding in 2020-2021, children were offered the alternate vaccine and were followed until 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, Month 18, Years 2, 4, and 5 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) of anti-Vi IgG was 2037.90 (95% CI: 1904.86-2180.23) at Day 28, dropping to 241.29 (220.27-264.31) at Month 18. At Year 5 post-vaccination, the GMC was 109.3 (98.65-121.10). The proportion of participants maintaining a ≥4-fold rise at Year 5 post-vaccination from baseline 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). CONCLUSIONS: 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. FUNDING: Wellcome Trust.