PMID- 28866290 OWN - NLM STAT- MEDLINE DCOM- 20180312 LR - 20180403 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 35 IP - 40 DP - 2017 Sep 25 TI - Immunogenicity, safety and reactogenicity of the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in 2-17-year-old children with asplenia or splenic dysfunction: A phase 3 study. PG - 5331-5338 LID - S0264-410X(17)31127-1 [pii] LID - 10.1016/j.vaccine.2017.08.039 [doi] AB - BACKGROUND: Immunization with pneumococcal vaccines is an important prophylactic strategy for children with asplenia or splenic dysfunction, who are at high risk of bacterial infections (including S. pneumoniae). This study aimed to assess immunogenicity and safety of pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, GSK) in this at-risk population. METHODS: This phase III, multi-centre, open-label, controlled study, in which at-risk children with asplenia or splenic dysfunction were enrolled (age strata: 2-4, 5-10 and 11-17years), was conducted in Poland and the Russian Federation. For the 2-4years at-risk group, healthy age-matched children were enrolled as control. Unprimed children (not previously vaccinated with any pneumococcal vaccine) received 2 PHiD-CV doses (>/=2months apart) and pneumococcal vaccine-primed children received 1 dose. Immune responses were assessed pre-vaccination and one month post-each dose. Solicited and unsolicited adverse events (AEs) were recorded for 4 and 31days post-vaccination, respectively, and serious AEs (SAEs) throughout the study. RESULTS: Of 52 vaccinated children (18 at-risk primed, 28 at-risk unprimed and 6 control unprimed), 45 (18, 23 and 4, respectively) were included in the according-to-protocol cohort for immunogenicity. Post-vaccination (post-dose 1 in primed and post-dose 2 in unprimed children), for each vaccine pneumococcal serotype and vaccine-related serotype 6A all at-risk children had antibody concentrations >/=0.2microg/mL, and for vaccine-related serotype 19A at least 94.4%. Increases in antibody geometric mean concentrations were observed. For most serotypes, all at-risk children had post-vaccination opsonophagocytic activity (OPA) titers >/=8 and increases in OPA geometric mean titers were observed. No safety concerns were raised. One non-fatal SAE (respiratory tract infection, considered not vaccine-related) was reported by one at-risk unprimed child. CONCLUSION: PHiD-CV was immunogenic and well tolerated in 2-17-year-old children with asplenia or splenic dysfunction. Clinical Trial Registry: www.clinicaltrials.gov, NCT01746108. CI - Copyright (c) 2017. Published by Elsevier Ltd. FAU - Szenborn, L AU - Szenborn L AD - Department of Pediatrics and Infectious Diseases, Medical University Wroclaw, Chalubinskiego 2-2A, 50-368 Wroclaw, Poland. Electronic address: leszek.szenborn@umed.wroc.pl. FAU - Osipova, I V AU - Osipova IV AD - Departmental Clinical Hospital at Barnaul Railway Station, Molodiozhnaya st. 20, 656038 Barnaul, Russian Federation. Electronic address: i.v.osipova@gmail.com. FAU - Czajka, H AU - Czajka H AD - Infectious Diseases Outpatient Clinic, The St. Luis Provincial Specialist Children's Hospital, 2a Strzelecka St., 31-503 Krakow, Poland. Electronic address: hanna.czajka@onet.pl. FAU - Kharit, S M AU - Kharit SM AD - Scientific and Research Institute of Children's Infections, Prof. Popova st. 9, 197022, Saint-Petersburg, Russian Federation. Electronic address: kharit-s@mail.ru. FAU - Jackowska, T AU - Jackowska T AD - Department of Pediatrics, The Center of Postgraduate Medical Education, Marymoncka 99/103, 01-813 Warsaw, Poland. Electronic address: tjackowska@cmkp.edu.pl. FAU - Francois, N AU - Francois N AD - GSK, 20, Avenue Fleming, B-1300 Wavre, Belgium. Electronic address: nancy.a.francois@gsk.com. FAU - Habib, M A AU - Habib MA AD - GSK, 20, Avenue Fleming, B-1300 Wavre, Belgium. Electronic address: Ahsan.M.Habib@gsk.com. FAU - Borys, D AU - Borys D AD - GSK, 20, Avenue Fleming, B-1300 Wavre, Belgium. Electronic address: Dorota.D.Borys@gsk.com. LA - eng SI - ClinicalTrials.gov/NCT01746108 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20170831 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (PHiD-CV vaccine) RN - 0 (Pneumococcal Vaccines) RN - 0 (Vaccines, Conjugate) SB - IM MH - Adolescent MH - Child MH - Child, Preschool MH - Female MH - Heterotaxy Syndrome/*immunology MH - Humans MH - Male MH - Pneumococcal Infections/immunology/*prevention & control MH - Pneumococcal Vaccines/*therapeutic use MH - Streptococcus pneumoniae/immunology/pathogenicity MH - Vaccines, Conjugate/*therapeutic use OTO - NOTNLM OT - Asplenia OT - Immunogenicity OT - Pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) OT - Safety OT - Splenic dysfunction EDAT- 2017/09/04 06:00 MHDA- 2018/03/13 06:00 CRDT- 2017/09/04 06:00 PHST- 2017/05/05 00:00 [received] PHST- 2017/07/26 00:00 [revised] PHST- 2017/08/20 00:00 [accepted] PHST- 2017/09/04 06:00 [pubmed] PHST- 2018/03/13 06:00 [medline] PHST- 2017/09/04 06:00 [entrez] AID - S0264-410X(17)31127-1 [pii] AID - 10.1016/j.vaccine.2017.08.039 [doi] PST - ppublish SO - Vaccine. 2017 Sep 25;35(40):5331-5338. doi: 10.1016/j.vaccine.2017.08.039. Epub 2017 Aug 31.