An open-label, comparative, single dose, clinical Phase Ⅰ study to assess the safety and immunogenicity of typhoid conjugate vaccine (Vi-CRM197) in healthy Filipino adults

Abstract

An injectable typhoid conjugate vaccine (TCV) provides longer-lasting protection, requires fewer doses, and is suitable for children aged >2 years. In addition, TCV is preferred at most ages owing to its improved immunological properties as it overcomes the limitation of Vi polysaccharide vaccines. Here, we assessed the safety, tolerability, and immunogenicity of a TCV, Vi-CRM197, termed EuTCV, in an open-label clinical phase I study in healthy Filipino adults. This study was conducted in 75 healthy adults aged 18–45 years who were randomized in a 1:1:1 ratio based on the vaccines administered: EuTCV (Test), Typbar-TCV® (WHO prequalified vaccine) and Typhim Vi® (Vi polysaccharide vaccine). The study vaccines were administered at a dose of 25 µg of Vi-CRM197 conjugate by intramuscular injection as a single dose to each of the 25 participants/group, and their immunogenicity and overall safety were assessed for 42 days post-vaccination. All study participants (n = 25/group) completed the trial without dropouts. There were no deaths, SAEs, or events leading to premature withdrawal from the study. Anti-Vi IgG antibody titer (geometric mean titer) of EuTCV group on day 42 was 65.325 [95% CI (36.860, 115.771)], which was significantly higher than that of the WHO prequalified TCV [24.795, 95% CI (16.164, 38.033) p = 0.0055] and the Vi polysaccharide vaccine [7.998, 95% CI (3.800, 16.835) p < 0.0001]. Moreover, the seroconversion rate of EuTCV and Typbar-TCV® was 100%, but that of Typhim Vi® was only 84%. The IgG1–3 subclass titers and serum bactericidal assay results in the EuTCV group showed higher and better bactericidal capacity than the other groups. EuTCV was well tolerated and exhibited an acceptable safety profile in the study population. The Vi-CRM197 conjugate dose of 25 μg may be considered effective in terms of efficacy and safety.ClinicalTrials.gov registration number: NCT03956524.