Lot-to-lot consistency,safety and immunogenicity of 3 lots of Haemophilus influenzae type b conjugate vaccine: results from a phase III randomized,multicenter study in infants |
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| Institution: | 1. Kaiser Permanente Vaccine Study Center, 1 Kaiser Plaza, 16th Floor, Oakland, CA 94612, United States;2. GSK, 5 Crescent Drive, Philadelphia, PA 19112, United States;3. Utah Valley Pediatrics Timpanogos, 1355 N University Avenue, Provo, UT 84604, United States;4. Palmetto Pediatrics, 2781 Tricom Street, North Charleston, SC 29406, United States;5. State University of New York Upstate Medical University, 750 E Adams Street, Syracuse, NY 13210, United States;6. Wee Care Pediatrics, 1792 W 1700 S, Syracuse, UT 84075, United States;7. Oklahoma State University Center for Health Sciences, 1111 W 17th Street, Tulsa, OK 74107, United States;8. Pediatric Infectious Disease, Creighton University, 601 N 30th Street, Suite 6820, Omaha, NE 68131, United States;9. Gamble Research for Clinical Studies, Cincinnati Children''s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, United States;10. GSK, 20 Avenue Fleming, 1300 Wavre, Belgium;11. GSK, 2301 Renaissance Blvd, King of Prussia, PA 19406, United States;12. GSK, 1250 South Collegeville Road, Collegeville, PA 19426, United States |
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| Abstract: | BackgroundVaccination against Haemophilus influenzae type b (Hib) is included in routine pediatric immunization schedule in the United States. Previous vaccine shortages have created the need for additional options for Hib vaccination.MethodsThis phase III, randomized, multi-centered study (NCT01000974) evaluated the safety and immunogenicity of a monovalent tetanus toxoid-conjugate Hib vaccine (Hib-TT) compared to a monovalent (Hib-TT control) and a combination Hib-TT vaccine. We hierarchically assessed lot-to-lot consistency of 3 Hib-TT lots and non-inferiority of Hib-TT to Hib-TT control. We co-administered routine pediatric vaccines with Hib-TT vaccines at 2, 4, 6 months (primary vaccination) and 15–18 months of age (booster vaccination). We recorded adverse events (AEs) for 4 (solicited) and 31 days (unsolicited) post-vaccination and serious AEs (SAEs) throughout the study.ResultsOf 4009 enrolled children, 3086 completed booster phase. Lot-to-lot consistency was not demonstrated. The study met statistical criteria for non-inferiority of Hib-TT to Hib-TT control in terms of immune responses to Hib and co-administered vaccines’ antigens, but not in terms of participants achieving post-primary vaccination anti-PRP levels ≥1 µg/mL. Because of the hierarchical nature of the objectives, non-inferiority could not be established. In all groups, 92.5–96.7% and 99.6–100% of participants achieved anti-PRP levels ≥0.15 µg/mL, while 78.3–89.8% and 97.9–99.1% had anti-PRP levels ≥1 µg/mL, post-primary and post-booster vaccination, respectively. Immune responses to co-administered vaccines and reported incidence of AEs were comparable among groups. We recorded SAEs for 107/2963 (3.6%), 24/520 (4.6%), and 21/520 (4.0%) children post-primary vaccination, and 29/2337 (1.2%), 4/435 (0.9%), and 2/400 (0.5%) children post-booster vaccination with Hib-TT, Hib-TT control and combination Hib-TT vaccine, respectively; 6/5330 (0.1%) SAEs in the Hib-TT groups were considered vaccine-related.ConclusionHib-TT induced seroprotective antibody concentrations in the majority of participants and was well-tolerated when co-administered with routine pediatric vaccines according to a 3 + 1 schedule. |
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| Keywords: | Primary immunization Booster Infants |
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