Live attenuated tetravalent (G1-G4) bovine-human reassortant rotavirus vaccine (BRV-TV): Randomized,controlled phase III study in Indian infants |
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| Institution: | 1. Shantha Biotechnics Pvt. Ltd., Hyderabad, India;2. Bharati Vidyapeeth Deemed University Medical College, Pune, India;3. All India Institute of Medical Sciences, New Delhi, India;4. Post Graduate Institute of Medical Education & Research, Chandigarh, India;5. King George Hospital, Visakhapatnam, India;6. Indira Gandhi Medical College, Shimla, India;7. JSS University, Mysore, India;8. Dr. TMA Pai Rotary Hospital, Karkala, India;9. J N Medical College, Belgaum, India;10. Padmashree Dr. D. Y. Patil Medical College & Research Center, Pune, India;11. KPC Medical College & Hospital, Kolkata, India;12. Pt. Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, India;13. Kanchi Kamakoti Child Trust Hospital & The Child Trust Medical Research Foundation, Chennai, India;14. Christian Medical College, Vellore, Tamil Nadu, India;15. Sanofi Pasteur, Marcy-l''Étoile, France;p. Sanofi Pasteur, Swiftwater, USA;1. Vaccine and Infectious Disease Research Centre, Translational Health Science and Technology Institute, Gurgaon 122016, India;2. Fogarty International Centre, NIH, Bethesda, MD 20892, USA;3. Society for Applied Studies, New Delhi 110016, India;4. Clinical Development Services Agency, Translational Health Science and Technology Institute, Gurgaon 122016, India;5. National Institute of Immunology, New Delhi 110067, India;1. Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville 22908, USA;2. Center for Vaccine Science and Parasitology Lab, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka 1212, Bangladesh;3. Vaccine Testing Center and Unit of Infectious Diseases, Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05405, USA;4. Center for Public Health Genomics, University of Virginia, Charlottesville 22908, USA;1. Indian Veterinary Research Institute, Izatnagar 243122, Uttar Pradesh, India;2. Department of Hygiene, Sapporo Medical University School of Medicine, S 1, W 17, Chuo-Ku, Sapporo, Hokkaido 060-8556, Japan;3. Institute for Veterinary Medical Research, Centre for Agricultural Research, Hungarian Academy of Sciences, Hungária krt. 21, Budapest 1143, Hungary;4. National Institute of Cholera and Enteric Diseases (NICED), Kolkata, West Bengal, India;5. Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan;6. Laboratory for Clinical and Epidemiological Virology, KU Leuven, REGA Institute, Minderbroedersstraat 10, B3000 Leuven, Belgium;1. Centre for Health Research and Development, Society for Applied Studies, 45 Kalu Sarai, New Delhi 110016, India;2. Innlandet Hospital Trust, Lillehammer, Norway;3. Centre for Intervention Science in Maternal and Child Health, Centre for International Health, University of Bergen, Norway;4. Department of Vaccines, Division of Infectious Disease Control, Norwegian Institute of Public Health Oslo, Norway;5. Department of Infectious Diseases Epidemiology, Division of Infectious Disease Control, Norwegian Institute of Public Health Oslo, Norway;6. The Wellcome Trust Research Laboratory, Christian Medical College, Vellore 632004, Tamil Nadu, India;7. Department of International Public Health, Norwegian Institute of Public Health, Oslo, Norway;8. Department of Virology, Division of Infectious Disease Control, Norwegian Institute of Public Health Oslo, Norway |
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| Abstract: | BackgroundRotavirus remains the leading cause of diarrhoea among children <5 years. We assessed immunogenic non-inferiority of a tetravalent bovine-human reassortant rotavirus vaccine (BRV-TV) over the licensed human-bovine pentavalent rotavirus vaccine RV5.MethodsPhase III single-blind study (parents blinded) in healthy infants randomized (1:1) to receive three doses of BRV-TV or RV5 at 6–8, 10–12, and 14–16 weeks of age. All concomitantly received a licensed diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b conjugate vaccine (DTwP-HepB-Hib) and oral polio vaccine (OPV). Immunogenic non-inferiority was evaluated in terms of the inter-group difference in anti-rotavirus serum IgA seroresponse (primary endpoint), and seroprotection/seroresponse rates to DTwP-HepB-Hib and OPV vaccines. Seroresponse was defined as a ≥4-fold increase in titers from baseline to D28 post-dose 3. Non-inferiority was declared if the difference between groups (based on the lower limit of the 95% confidence interval CI]) was above ?10%. Each subject was evaluated for solicited adverse events 7 days and unsolicited & serious adverse events 28 days following each dose of vaccination.ResultsOf 1195 infants screened, 1182 were randomized (590 to BRV-TV; 592 to RV5). Non-inferiority for rotavirus serum IgA seroresponse was not established: BRV-TV, 47.1% (95%CI: 42.8; 51.5) versus RV5, 61.2% (95%CI: 56.8; 65.5); difference between groups, ?14.08% (95%CI: ?20.4; ?7.98). Serum IgA geometric mean concentrations at D28 post-dose 3 were 28.4 and 50.1 U/ml in BRV-TV and RV5 groups, respectively. For all DTwP-HepB-Hib and OPV antigens, seroprotection/seroresponse was elicited in both groups and the ?10% non-inferiority criterion between groups was met. There were 16 serious adverse events, 10 in BRV-TV group and 6 in RV5 group; none were classified as vaccine related. Both groups had similar vaccine safety profiles.ConclusionBRV-TV was immunogenic but did not meet immunogenic non-inferiority criteria to RV5 when administered concomitantly with routine pediatric antigens in infants. |
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| Keywords: | Rotavirus vaccine Bovine-human reassortant rotavirus vaccine BRV-TV Seroresponse Immunogenicity Safety Immune non-inferiority |
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