AUTHORS
Nginache Nampota-Nkomba, Osward M. Nyirenda, Shrimati Datta, Victoria Mapemba, Priyanka D. Patel, Theresa Misiri, Felistas Mwakiseghile, John M. Ndaferankhande, Bright Lipenga, Jennifer Oshinsky, Marcela F. Pasetti, Leslie P. Jamka, Melita A. Gordon, Matthew B. Laurens, Kathleen M. Neuzil, TyVAC team
ABSTRACT
Background
We assessed persistence of typhoid immunity conferred by Vi polysaccharide-tetanus toxoid (Vi-TT) conjugate vaccine (TCV) four years post-vaccination and immunogenicity of a booster dose of Vi-TT given at age five.
Methods
In 2018, a phase 3 trial of Vi-TT in Malawi randomised children 1:1 to receive Vi-TT or meningococcal capsular group A conjugate vaccine (control). Subsequently, TCV was licensed and recommended in the region. In 2023, children vaccinated at 9–11 months in the original trial received a second (Booster- TCV) or first (1st-TCV) Vi-TT dose, at age five. Serum collected at days 0, 28, and 160–180 days after vaccination was tested for anti-Vi immunoglobulin (Ig)G and IgA, reported as enzyme-linked immunosorbent assay units (EU)/mL. Seroconversion was ≥4-fold rise in antibody titers from day 0 to day 28 post-vaccination. Safety outcomes included adverse events during follow-up.
Findings
We enrolled 136 children: 72 Booster-TCV and 64 1st-TCV. At baseline, anti-Vi IgG geometric mean titers (GMT) were higher in Booster-TCV (18.8 EU/mL, 95% CI 15.2–23.2) than 1st-TCV (5.7 EU/mL, 4.6–7.2) arms. GMT increased significantly between days 0 and 28 in both arms, with higher levels in Booster-TCV (6867.9 EU/mL, 5794.1–8140.6) than 1st-TCV (2912.0 EU/mL, 2429.2–3490.7) arms, representing a 375.7 and 492.6 geometric mean fold rise, respectively. On day 28, all Booster-TCV children, and all but one 1st-TCV child, seroconverted. Similar trends were seen for IgA. Vi-TT reactogenicity was similar between vaccine arms.
Interpretation
This study demonstrates sustained Vi-TT immunogenicity four years post-vaccination at 9–11 months old, and robust immune response following a booster dose at five years of age, informing policy decisions on TCV use in children.
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