PMID- 27133877 OWN - NLM STAT- MEDLINE DCOM- 20171023 LR - 20201209 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 34 IP - 27 DP - 2016 Jun 8 TI - Phase I, randomized, observer-blind, placebo-controlled studies to evaluate the safety, reactogenicity and immunogenicity of an investigational non-typeable Haemophilus influenzae (NTHi) protein vaccine in adults. PG - 3156-3163 LID - S0264-410X(16)30205-5 [pii] LID - 10.1016/j.vaccine.2016.04.051 [doi] AB - BACKGROUND: Non-typeable Haemophilus influenzae (NTHi) is a major cause of various respiratory diseases. The development of an effective vaccine against NTHi mandates new approaches beyond conjugated vaccines as this opportunistic bacterium is non-encapsulated. Here we report on the safety, reactogenicity and immunogenicity of a multi-component investigational vaccine based on three conserved surface proteins from NTHi (proteins D [PD], E [PE] and Pilin A [PilA]) in two observer-blind phase I studies. METHODS: In the first study (NCT01657526), 48 healthy 18-40 year-olds received two vaccine formulations (10 or 30mug of each antigen [PD and a fusion protein PE-PilA]) or saline placebo at months 0 and 2. In the second study (NCT01678677), 270 50-70 year-olds, current or former smokers, received eight vaccine formulations (10 or 30mug antigen/dose non-adjuvanted or adjuvanted with alum, AS01E or AS04C) or saline placebo at months 0, 2 and 6 (plain and alum-adjuvanted groups) and at months 0 and 2 (AS-adjuvanted groups). Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days post-vaccination, respectively; potential immune-mediated diseases (pIMDs) and serious AEs (SAEs) throughout the studies. Humoral and antigen-specific T-cell immunity (in study 2 only) responses were assessed up to 12 months post-vaccination. RESULTS: Observed reactogenicity was highest in the AS-adjuvanted groups but no safety concerns were identified with any of the NTHi vaccine formulations. One fatal SAE (cardiac arrest) not considered related to vaccination, and one pIMD (non-serious psoriasis) in the Placebo group, were reported post-dose 3 in Study 2. All formulations generated a robust antibody response while the AS01-adjuvanted formulations produced the highest humoral and cellular immune responses. CONCLUSION: This study confirms that the NTHi vaccine formulations had an acceptable reactogenicity and safety profile and were immunogenic in adults. These results justify further clinical development of this NTHi vaccine candidate. CI - Copyright (c) 2016 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Leroux-Roels, Geert AU - Leroux-Roels G AD - Center for Vaccinology, Ghent University and Ghent University Hospital, BC001, De Pintelaan 185, B-9000 Ghent, Belgium. Electronic address: Geert.LerouxRoels@UGent.be. FAU - Van Damme, Pierre AU - Van Damme P AD - Centre for the Evaluation of Vaccination, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610 Antwerp, Belgium. Electronic address: pierre.vandamme@uantwerpen.be. FAU - Haazen, Wouter AU - Haazen W AD - SGS Life Sciences Services, Lange Beeldekensstraat 267, 2060 Antwerp, Belgium. Electronic address: wouter.haazen1@telenet.be. FAU - Shakib, Sepehr AU - Shakib S AD - University of Adelaide, Mail Delivery Point 22, Royal Adelaide Hospital, North Terrace, 5000 Adelaide, Australia. Electronic address: sepehr.shakib@sa.gov.au. FAU - Caubet, Magalie AU - Caubet M AD - GSK Vaccines, Rue de l'Institut 89, 1330 Rixensart, Belgium. Electronic address: magalie.caubet@gsk.com. FAU - Aris, Emmanuel AU - Aris E AD - GSK Vaccines, Rue de l'Institut 89, 1330 Rixensart, Belgium. Electronic address: emmanuel.x.aris@gsk.com. FAU - Devaster, Jeanne-Marie AU - Devaster JM AD - GSK Vaccines, Rue de l'Institut 89, 1330 Rixensart, Belgium. Electronic address: jeanne-marie.devaster@gsk.com. FAU - Peeters, Mathieu AU - Peeters M AD - GSK Vaccines, Rue de l'Institut 89, 1330 Rixensart, Belgium. Electronic address: Mathieu.peeters@yahoo.co.uk. LA - eng PT - Clinical Trial, Phase I PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20160429 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Adjuvants, Immunologic) RN - 0 (Antibodies, Viral) RN - 0 (Haemophilus Vaccines) RN - 0 (Vaccines, Conjugate) SB - IM EIN - Vaccine. 2017 Oct 9;35(42):5729-5730. PMID: 28882439 MH - Adjuvants, Immunologic/administration & dosage MH - Adult MH - Aged MH - Antibodies, Viral/blood MH - Australia MH - Belgium MH - Female MH - Haemophilus Infections/*prevention & control MH - Haemophilus Vaccines/immunology/*therapeutic use MH - Haemophilus influenzae MH - Humans MH - Immunity, Cellular MH - Immunity, Humoral MH - Male MH - Middle Aged MH - Single-Blind Method MH - Vaccines, Conjugate MH - Young Adult OTO - NOTNLM OT - Adjuvant OT - Adult vaccination OT - Immunogenicity OT - NTHi OT - Safety EDAT- 2016/05/03 06:00 MHDA- 2017/10/24 06:00 CRDT- 2016/05/03 06:00 PHST- 2016/02/02 00:00 [received] PHST- 2016/04/13 00:00 [revised] PHST- 2016/04/18 00:00 [accepted] PHST- 2016/05/03 06:00 [entrez] PHST- 2016/05/03 06:00 [pubmed] PHST- 2017/10/24 06:00 [medline] AID - S0264-410X(16)30205-5 [pii] AID - 10.1016/j.vaccine.2016.04.051 [doi] PST - ppublish SO - Vaccine. 2016 Jun 8;34(27):3156-3163. doi: 10.1016/j.vaccine.2016.04.051. Epub 2016 Apr 29.