Bakul Javadekar1, Apurba Ghosh2, Rajeev Zachariah Kompithra3, Shally Awasthi4, Olga Perminova5, Viktor Romanenko6, Vera Rodnikova7, Susanna Kharit8, Yael Thollot9, Valerie Bosch-Castells10, Alexander Goldstein11, Himanshu Dubey12. 1. Department of Pediatrics, Medical College and SSG Hospital, Baroda, SSG Hospital Campus, Raopura, Vadodara, Gujarat, India. 2. Institute of Child Health, Kolkata, West Bengal, India. 3. Well Baby Clinic, Department of Child Health, Christian Medical College, Vellore, Tamilnadu, India. 4. Department of Pediatrics, Shahuji Maharaj Medical University, Lucknow, Uttar Pradesh, India. 5. City Children's Policlinic No 5, Perm, Russia. 6. Municipal City Children Hospital #11, Ekaterinburg, Russia. 7. Murmansk Children's City Hospital, Murmansk, Russia. 8. Research Institute for Pediatric Infectious Diseases, St. Petersburg, Russia. 9. Sanofi Pasteur, Lyon, France. 10. Sanofi Pasteur, Marcy l'Etoile, France. 11. Sanofi Pasteur, Moscow, Russia. 12. Medical Affairs, Sanofi Pasteur, Mumbai, India. Correspondence to: Dr Himanshu Dubey, Sanofi House, CTS No. 117-B, L and T Business Park, Saki Vihar Road, Powai, Mumbai 400 072, India. Himanshu.Dubey@sanofi.com.
Abstract
OBJECTIVE: Evaluation of tolerability, safety and immunogenicity of a two-dose series of a quadrivalent meningococcal polysaccharide diptheria toxoid conjugate (ACYW-D) vaccine in Indian and Russian infants/toddlers. DESIGN: Open-label, single-arm, phase III multi-national trial. STUDY PARTICIPANTS: 300 children aged 9-17 months, previously unvaccinated against meningococcal disease from four sites each in India (n=200) and the Russian Federation (n=100). INTERVENTION: Two 0.5 mL doses of ACYW-D by intramuscular injection, 3-6 months apart. MAIN OUTCOME MEASURES: Meningococcal antibody titers to serogroups A, C, W-135 and Y, determined using a serum bactericidal assay in the presence of human complement before vaccination and 28 days after the second vaccination. Titers ≥1:8 against either/all of the A, C, W-135 or Y were considered sero-protective. RESULTS: After dose 2, 95.7-99.5% and 92.9-99.0% of infants/toddlers achieved seroprotection across the four serogroups in India and the Russian Federation, respectively. No immediate adverse events were reported after any dose of ACYW-D. Solicited reactions were reported in 49.2% of participants, and were mainly of Grade 1 severity, and resolved within three days. Unsolicited adverse events were reported in 19.1% of infants: one event (Grade 3 diarrhea, resolving within one day) was considered related to study vaccine. No non-serious adverse events led to premature withdrawal from the study. Four serious adverse events were reported; none were considered related to study vaccine. No deaths occurred during the study. CONCLUSIONS: A two-dose series of ACYW-D vaccine in Indian and Russian children (9-17 month) was well-tolerated with no safety concerns, and induced robust bactericidal antibody responses against the meningococcal serogroups contained in the vaccine.
OBJECTIVE: Evaluation of tolerability, safety and immunogenicity of a two-dose series of a quadrivalent meningococcalpolysaccharide diptheria toxoid conjugate (ACYW-D) vaccine in Indian and Russian infants/toddlers. DESIGN: Open-label, single-arm, phase III multi-national trial. STUDY PARTICIPANTS: 300 children aged 9-17 months, previously unvaccinated against meningococcal disease from four sites each in India (n=200) and the Russian Federation (n=100). INTERVENTION: Two 0.5 mL doses of ACYW-D by intramuscular injection, 3-6 months apart. MAIN OUTCOME MEASURES: Meningococcal antibody titers to serogroups A, C, W-135 and Y, determined using a serum bactericidal assay in the presence of human complement before vaccination and 28 days after the second vaccination. Titers ≥1:8 against either/all of the A, C, W-135 or Y were considered sero-protective. RESULTS: After dose 2, 95.7-99.5% and 92.9-99.0% of infants/toddlers achieved seroprotection across the four serogroups in India and the Russian Federation, respectively. No immediate adverse events were reported after any dose of ACYW-D. Solicited reactions were reported in 49.2% of participants, and were mainly of Grade 1 severity, and resolved within three days. Unsolicited adverse events were reported in 19.1% of infants: one event (Grade 3 diarrhea, resolving within one day) was considered related to study vaccine. No non-serious adverse events led to premature withdrawal from the study. Four serious adverse events were reported; none were considered related to study vaccine. No deaths occurred during the study. CONCLUSIONS: A two-dose series of ACYW-D vaccine in Indian and Russian children (9-17 month) was well-tolerated with no safety concerns, and induced robust bactericidal antibody responses against the meningococcal serogroups contained in the vaccine.