Immunogenicity and Safety of Typhoid Conjugate Vaccine in Healthy Indian Subjects: A Randomized, Active-controlled, Comparative Clinical Trial

Abstract

To compare the immunogenicity and safety of an investigational typhoid Vi conjugate vaccine (Test TCV) with a marketed typhoid Vi conjugate vaccine (Comparator TCV). Randomized, controlled trial. Tertiary care and multispecialty hospitals. 240 healthy subjects of 6 months to 45 years. Pediatric (<18 years) subjects were enrolled after day 21 safety assessment of adult subjects. Participants received a single-dose of test TCV or comparator TCV at baseline and were followed up for 6 weeks post-vaccination. Primary variable was to demonstrate non-inferiority of the test TCV with the comparator TCV for seroconversion post-vaccination (³4-fold rise in antibody titre). Secondary variables were seroconversion in the adult and pediatric cohorts, and geometric mean titre of antibodies while the safety was based on reported adverse events. A total of 117 subjects (Adult-58, Pediatric-59) and 119 subjects (Adult-60, Pediatric-59) in test and comparator group, respectively completed the study. The seroconversion rate with test TCV (overall-94.8%, adult-96.6% and pediatric-93.1%) was non-inferior to comparator TCV (overall-91.6%, adult-91.7% and pediatric-91.5%). The geometric mean titres of antibodies (EU/mL) at baseline (test TCV: overall-7.6, adult-10.0, and pediatric-5.7; and comparator TCV: overall-8.0, adult-12.0, and pediatric-5.3) and at end of study (test TCV: overall-1121.0, adult-1411.0 and pediatric-891.1; and comparator TCV: overall-1104.0, adult-1199.0 and pediatric-1014.0) were also comparable between the groups (P>0.05 for all). The most common adverse event was injection-site pain followed by fever in both the groups. The immunogenicity and safety of test TCV is comparable to already marketed comparator TCV.