A comparative study to evaluate the safety and immunogenicity of two lots of Haemophilus influenzae type-B conjugate vaccine manufactured at different scales

Abstract

ObjectiveTo compare the immunogenicity and safety of two different lots of SII Haemophilus influenzae type-B–tetanus toxoid conjugate (SII HibPRO) vaccine manufactured at different scales when given in 3-dose schedule. DesignPhase IV, open label, comparative, randomized parallel group study. SettingShirdi Sai Baba Hospital, Vadu Budruk, Pune and Pediatrics Department of King Edward Memorial Hospital Research Centre, Pune. Subjects204 normal healthy infants of age 6–8 weeks at the time of first vaccination. MethodsThe eligible subjects received 3 doses of 0.5ml of SII HibPRO vaccine of either lot depending upon randomization number, intramuscularly in right thigh in the EPI schedule of 6, 10 and 14 weeks. They also received concomitantly DTP-HB vaccine intramuscularly on left thigh and Oral Polio vaccine (OPV). Solicited reactions were captured for 7 days following each vaccination; the events beyond 7 days till day 28 were captured as unsolicited adverse events. Serious Adverse Events (SAEs) were looked for throughout the subject participation. Blood samples were collected at baseline (before the first dose) and one month after the third dose for anti-PRP (polyribosylribitol phosphate) antibodies. ResultsIn both groups, more than 98% subjects achieved short-term seroprotection (anti-PRP≥0.15μg/ml) after 3 doses. The long-term seroprotection (anti-PRP≥1μg/ml) was 87% and 80% in infants receiving lot manufactured at industrial scale and small scale respectively. Short and long term seroprotection and GMTs increased significantly as compared to baseline in both the groups. Overall local pain (52% and 58%), redness (30% and 41%), swelling (34% and 44%), fever (6% and 6%) and irritability (52% and 50%) were reported in infants receiving lot manufactured at industrial scale and small scale respectively. Majority of the reactions were mild and resoled without any sequelae. Four SAEs, none of them causally related to the study vaccine, occurred during study. ConclusionSII HibPRO vaccines manufactured in small and industrial scale are equally immunogenic, safe and confer adequate seroprotection to infants of 6–14 weeks of age. Scaling up production process has not affected the safety and immune response in the target population.