PMID- 29277353 OWN - NLM STAT- MEDLINE DCOM- 20180918 LR - 20180918 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 36 IP - 5 DP - 2018 Jan 29 TI - Immunologic non-inferiority and safety of the investigational pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) 4-dose vial presentation compared to the licensed PHiD-CV 1-dose vial presentation in infants: A phase III randomized study. PG - 698-706 LID - S0264-410X(17)31787-5 [pii] LID - 10.1016/j.vaccine.2017.12.034 [doi] AB - BACKGROUND: To support vaccination programs in developing countries, a 4-dose vial presentation of pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) was developed. This study assessed immunologic non-inferiority and safety of the investigational PHiD-CV 4-dose versus licensed 1-dose vial presentation in infants. METHODS: In this phase III, mono-center, observer-blind study in Bangladesh, 6-10-week-old infants were randomized 1:1 to receive PHiD-CV primary vaccination (at ages 6, 10, 18 weeks) and a booster dose (at age 9 months) with a 4-dose vial (with preservative, 4DV group) or 1-dose vial (preservative-free, 1DV group). DTPw-HBV/Hib was (co)-administered per study protocol and polio, measles and rubella vaccines as part of the national immunization program. Non-inferiority of PHiD-CV 4-dose versus 1-dose vial for each vaccine pneumococcal serotype (VT) and vaccine-related serotype 19A in terms of antibody geometric mean concentration (GMC) was assessed (criterion: upper limit of 2-sided 95% confidence interval of antibody GMC ratios [1DV/4DV] <2-fold). Immune responses were measured. Solicited, unsolicited and serious adverse events (AEs) were evaluated. RESULTS: Of 320 infants (160 per group) vaccinated during the primary vaccination phase, 297 received a booster. Non-inferiority was demonstrated for each VT and 19A. One month post-primary vaccination, for most VT, >/=97.9% of infants in each group had antibody concentrations >/=0.2 mug/mL; for 19A >/= 80.1% reached this threshold. Pneumococcal antibody responses and opsonophagocytic activity for each VT and 19A were within similar ranges between groups after primary and booster vaccination, as were anti-protein D responses. Booster immune responses were observed in both groups. Reported AEs were within similar ranges for both presentations. CONCLUSION: Immunologic non-inferiority of PHiD-CV 4-dose vial (with preservative) versus PHiD-CV 1-dose vial (preservative-free) was demonstrated. Immune responses and reactogenicity following primary/booster vaccination were within similar ranges for both presentations. PHiD-CV 4-dose vial would help improve access and coverage in resource-limited countries. Clinical Trial Registry: NCT02447432. CI - Copyright (c) 2017. Published by Elsevier Ltd. FAU - Zaman, Khalequ AU - Zaman K AD - International Centre for Diarrheal Disease Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka 1212, Bangladesh. Electronic address: kzaman@icddrb.org. FAU - Zaman, Sheikh Farzana AU - Zaman SF AD - International Centre for Diarrheal Disease Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka 1212, Bangladesh. Electronic address: sfzaman@icddrb.org. FAU - Zaman, Farzana AU - Zaman F AD - International Centre for Diarrheal Disease Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka 1212, Bangladesh. Electronic address: drlisa83@yahoo.co.in. FAU - Aziz, Asma AU - Aziz A AD - International Centre for Diarrheal Disease Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka 1212, Bangladesh. Electronic address: asma.aziz@icddrb.org. FAU - Faisal, Sayeed-Bin AU - Faisal SB AD - International Centre for Diarrheal Disease Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka 1212, Bangladesh. Electronic address: sayeed.faisal@icddrb.org. FAU - Traskine, Magali AU - Traskine M AD - GSK, 20 Avenue Fleming, B-1300 Wavre, Belgium. Electronic address: magali.x.traskine@gsk.com. FAU - Habib, Md Ahsan AU - Habib MA AD - GSK, 20 Avenue Fleming, B-1300 Wavre, Belgium. Electronic address: Ahsan.M.Habib@gsk.com. FAU - Ruiz-Guinazu, Javier AU - Ruiz-Guinazu J AD - GSK, 20 Avenue Fleming, B-1300 Wavre, Belgium. Electronic address: javier.x.ruiz@gsk.com. FAU - Borys, Dorota AU - Borys D AD - GSK, 20 Avenue Fleming, B-1300 Wavre, Belgium. Electronic address: Dorota.D.Borys@gsk.com. LA - eng SI - ClinicalTrials.gov/NCT02447432 PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20171223 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Antibodies, Bacterial) RN - 0 (PHiD-CV vaccine) RN - 0 (Pneumococcal Vaccines) SB - IM MH - Antibodies, Bacterial/blood/immunology MH - Female MH - Humans MH - Immunization, Secondary MH - *Immunogenicity, Vaccine MH - Infant MH - Infant, Newborn MH - Male MH - Pneumococcal Infections/*epidemiology/*prevention & control MH - Pneumococcal Vaccines/*administration & dosage/adverse effects/*immunology MH - Public Health Surveillance MH - Serogroup MH - Streptococcus pneumoniae/*immunology MH - Vaccination OTO - NOTNLM OT - 1-dose vial presentation OT - 4-dose vial presentation OT - Immunologic non-inferiority OT - Infants OT - Pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) OT - Safety EDAT- 2017/12/27 06:00 MHDA- 2018/09/19 06:00 CRDT- 2017/12/27 06:00 PHST- 2017/07/22 00:00 [received] PHST- 2017/12/11 00:00 [revised] PHST- 2017/12/12 00:00 [accepted] PHST- 2017/12/27 06:00 [pubmed] PHST- 2018/09/19 06:00 [medline] PHST- 2017/12/27 06:00 [entrez] AID - S0264-410X(17)31787-5 [pii] AID - 10.1016/j.vaccine.2017.12.034 [doi] PST - ppublish SO - Vaccine. 2018 Jan 29;36(5):698-706. doi: 10.1016/j.vaccine.2017.12.034. Epub 2017 Dec 23.