INTRODUCTION: Diphtheria is a serious infectious disease although being vaccine-preventable. 5-year follow-up study aimed to evaluate the persistence of IgG antibodies to diphtheria toxoid after Tetanus-diphtheria primary immunization for persons aged 6-25 years in Kon Tum, Viet Nam. METHODOLOGY: Blood samples were obtained from 128 healthy persons aged 6-25 years collected in 2021. Samples were tested for diphtheria toxoid antibodies by commercial Anti-Diphtheria Toxoid IgG Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: One month after Td primary vaccination, 92.2% of participants were fully protected against diphtheria (>
0.1 IU/mL). GMCs increased from 0.04 to 0.91 IU/mL at one month, which were maintained in nearly 90% of vaccinees at 5 years. Among children aged 6-10 years, 97.3% had full protection at 1 month after primary vaccination, maintained in 94.6% at 5 years. Among adolescents and adults, 81.0% to 98.5% had full protection at 1 month after vaccination, which were maintained from 72.7% to 96.7% at 5 years. Although, the antibodies slightly declined approximately 5 years post-vaccination, but remained several-fold higher than pre-vaccination. CONCLUSIONS: Td vaccine provides long-lasting protective antibodies against diphtheria. These data may inform discussion of the need for Td booster vaccinations among high-risk persons.