PMID- 28536030 OWN - NLM STAT- MEDLINE DCOM- 20180226 LR - 20190107 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 35 IP - 28 DP - 2017 Jun 16 TI - 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. PG - 3564-3574 LID - S0264-410X(17)30626-6 [pii] LID - 10.1016/j.vaccine.2017.05.018 [doi] AB - BACKGROUND: Vaccination 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. METHODS: This 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, 6months (primary vaccination) and 15-18months of age (booster vaccination). We recorded adverse events (AEs) for 4 (solicited) and 31days (unsolicited) post-vaccination and serious AEs (SAEs) throughout the study. RESULTS: Of 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 >/=1microg/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 >/=0.15microg/mL, while 78.3-89.8% and 97.9-99.1% had anti-PRP levels >/=1microg/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. CONCLUSION: Hib-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. CI - Copyright (c) 2017 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Klein, Nicola P AU - Klein NP AD - Kaiser Permanente Vaccine Study Center, 1 Kaiser Plaza, 16th Floor, Oakland, CA 94612, United States. Electronic address: Nicola.Klein@kp.org. FAU - Abu-Elyazeed, Remon AU - Abu-Elyazeed R AD - GSK, 5 Crescent Drive, Philadelphia, PA 19112, United States. FAU - Cornish, Matthew AU - Cornish M AD - Utah Valley Pediatrics Timpanogos, 1355 N University Avenue, Provo, UT 84604, United States. FAU - Leonardi, Michael L AU - Leonardi ML AD - Palmetto Pediatrics, 2781 Tricom Street, North Charleston, SC 29406, United States. FAU - Weiner, Leonard B AU - Weiner LB AD - State University of New York Upstate Medical University, 750 E Adams Street, Syracuse, NY 13210, United States. FAU - Silas, Peter E AU - Silas PE AD - Wee Care Pediatrics, 1792 W 1700 S, Syracuse, UT 84075, United States. FAU - Grogg, Stanley E AU - Grogg SE AD - Oklahoma State University Center for Health Sciences, 1111 W 17th Street, Tulsa, OK 74107, United States. FAU - Varman, Meera AU - Varman M AD - Pediatric Infectious Disease, Creighton University, 601 N 30th Street, Suite 6820, Omaha, NE 68131, United States. FAU - Frenck, Robert W AU - Frenck RW AD - Gamble Research for Clinical Studies, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, United States. FAU - Cheuvart, Brigitte AU - Cheuvart B AD - GSK, 20 Avenue Fleming, 1300 Wavre, Belgium. FAU - Baine, Yaela AU - Baine Y AD - GSK, 2301 Renaissance Blvd, King of Prussia, PA 19406, United States. FAU - Miller, Jacqueline M AU - Miller JM AD - GSK, 2301 Renaissance Blvd, King of Prussia, PA 19406, United States. FAU - Leyssen, Maarten AU - Leyssen M AD - GSK, 20 Avenue Fleming, 1300 Wavre, Belgium. FAU - Mesaros, Narcisa AU - Mesaros N AD - GSK, 20 Avenue Fleming, 1300 Wavre, Belgium. FAU - Roy-Ghanta, Sumita AU - Roy-Ghanta S AD - GSK, 1250 South Collegeville Road, Collegeville, PA 19426, United States. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20170520 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Antibodies, Bacterial) RN - 0 (Haemophilus Vaccines) RN - 0 (Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate) RN - 0 (Haemophilus influenzae type b polysaccharide vaccine) RN - 0 (Tetanus Toxoid) RN - 0 (Vaccines, Conjugate) RN - C9R35M8XV6 (Hiberix) SB - IM MH - Antibodies, Bacterial/blood MH - Bacterial Capsules/immunology MH - Female MH - Haemophilus Infections/epidemiology/immunology/*prevention & control MH - Haemophilus Vaccines/administration & dosage/*adverse effects/chemistry/*immunology MH - Haemophilus influenzae type b/immunology MH - Humans MH - Immunization Schedule MH - Immunization, Secondary MH - Immunogenicity, Vaccine MH - Infant MH - Male MH - Tetanus Toxoid/administration & dosage/adverse effects/immunology MH - United States/epidemiology MH - Vaccines, Conjugate/administration & dosage/adverse effects/chemistry/immunology OTO - NOTNLM OT - Booster OT - Haemophilus influenzae type b OT - Hiberix OT - Infants OT - Primary immunization EDAT- 2017/05/26 06:00 MHDA- 2018/02/27 06:00 CRDT- 2017/05/25 06:00 PHST- 2017/01/09 00:00 [received] PHST- 2017/05/02 00:00 [revised] PHST- 2017/05/07 00:00 [accepted] PHST- 2017/05/26 06:00 [pubmed] PHST- 2018/02/27 06:00 [medline] PHST- 2017/05/25 06:00 [entrez] AID - S0264-410X(17)30626-6 [pii] AID - 10.1016/j.vaccine.2017.05.018 [doi] PST - ppublish SO - Vaccine. 2017 Jun 16;35(28):3564-3574. doi: 10.1016/j.vaccine.2017.05.018. Epub 2017 May 20.