Immunogenicity and tolerability of a heterologous booster typhoid conjugate vaccine (TCV) five to six years after primary vaccination in Burkinabe Children: An open-label, non-randomized follow-up of a phase 2 trial cohort

Typhoid fever remains a major public health challenge in low- and middle-income countries. In 2018, the World Health Organization recommended a single dose of typhoid conjugate vaccine (TCV) for routine immunization in endemic settings; however, evidence to inform booster dosing remains limited. This study evaluated the immunogenicity and safety of a heterologous booster strategy using a Vi capsular polysaccharide-CRM197 TCV (Vi-CRM) administered 5–6 years after primary vaccination with a Vi capsular polysaccharide tetanus toxoid TCV (Vi-TT). In this open-label, non-randomized follow-up study, children previously enrolled in a Phase 2 randomized trial in Ouagadougou, Burkina Faso, were re-enrolled. Participants who had received TCV at 9–11 or 15–23 months of age received a Vi-CRM booster at 6–7 years of age (Booster-TCV group), while control participants received their first TCV dose at the same age (1st-TCV group). Group assignment reflected allocation in the parent trial; no new randomization was performed. Serum anti-Vi IgG concentrations were measured before vaccination and 28 days afterward. Seroconversion was defined as a ≥ 4-fold increase from baseline. Solicited and unsolicited adverse events (AEs) and serious adverse events (SAEs) were recorded. Among 147 enrolled children, 87 received a booster dose and 60 received a first TCV dose. Baseline anti-Vi IgG geometric mean titers (GMTs) were higher in the Booster-TCV group than in the 1st-TCV group (21.5 [95% CI, 17.2-26.8] vs 5.5 [95% CI, 4.5-6.8] EU/mL). By day 28, GMTs increased to 5140.0 (95% CI, 4302.0-6141.3) and 2084.8 (95% CI, 1724.4-2520.5) EU/mL, respectively, and all participants with evaluable samples seroconverted. Solicited reactions were infrequent and mild, and no SAEs occurred through day 28. These findings demonstrate robust immunogenicity and short-term tolerability of heterologous TCV boosting; however, because no correlate of protection exists for TCVs, the results do not establish sustained or post-booster clinical protection. Trial registration: ClinicalTrials.gov NCT07624175 (registered 2026-06-03); parent trial NCT03614533