PMID- 31447126 OWN - NLM STAT- MEDLINE DCOM- 20200928 LR - 20200928 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 37 IP - 41 DP - 2019 Sep 24 TI - Non-typeable Haemophilus influenzae protein vaccine in adults with COPD: A phase 2 clinical trial. PG - 6102-6111 LID - S0264-410X(19)31021-7 [pii] LID - 10.1016/j.vaccine.2019.07.100 [doi] AB - Loss of airway microbial diversity is associated with non-typeable Haemophilus influenzae (NTHi) infection and increased risk of exacerbation in chronic obstructive pulmonary disease (COPD). We assessed the safety and immunogenicity of an investigational vaccine containing NTHi antigens, recombinant protein D (PD) and combined protein E and Pilin A (PE-PilA), and AS01 adjuvant in adults with moderate/severe COPD and prior exacerbations. In this phase 2, observer-blind, controlled trial (NCT02075541), 145 COPD patients aged 40-80 years randomly (1:1) received two doses of NTHi vaccine or placebo 60 days apart, on top of standard care. Reactogenicity in the 7-day post-vaccination period was higher following NTHi vaccine than placebo. Most solicited adverse events (AEs) were mild/moderate. At least one unsolicited AE was reported during the 30-day post-vaccination period by 54.8% of NTHi vaccine and 51.4% of placebo recipients. One serious AE (placebo group) was assessed by the investigator as vaccine-related. Anti-PD, anti-PE and anti-PilA geometric mean antibody concentrations increased up to 30 days after each NTHi vaccine dose, waned thereafter, but remained higher than baseline (non-overlapping confidence intervals) up to 13 months post-dose 2. The frequency of specific CD4(+) T cells increased following two doses of NTHi vaccine and remained higher than baseline. Exploratory analysis showed a statistically non-significant lower yearly rate of moderate/severe exacerbations in the NTHi vaccine group than following placebo (1.49 versus 1.73) in the one-year period post-dose 2, with estimated vaccine efficacy of 13.3% (95% confidence interval -24.2 to 39.5; p = 0.44). The NTHi vaccine had an acceptable safety and reactogenicity profile and good immunogenicity in adults with COPD. CI - Copyright (c) 2019 GlaxoSmithKline Biologicals S.A. Published by Elsevier Ltd.. All rights reserved. FAU - Wilkinson, Tom M A AU - Wilkinson TMA AD - Clinical and Experimental Sciences, University of Southampton, Faculty of Medicine, Southampton General Hospital, Southampton, UK; Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Southampton, UK; Wessex Investigational Sciences Hub, University of Southampton, Faculty of Medicine, Southampton General Hospital, Southampton, UK. FAU - Schembri, Stuart AU - Schembri S AD - Scottish Centre for Respiratory Research, University of Dundee, Dundee, UK. FAU - Brightling, Christopher AU - Brightling C AD - Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK. FAU - Bakerly, Nawar D AU - Bakerly ND AD - Salford Royal NHS Foundation Trust, Salford, UK. FAU - Lewis, Keir AU - Lewis K AD - School of Medicine, University of Swansea, Wales, UK. FAU - MacNee, William AU - MacNee W AD - MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK. FAU - Rombo, Lars AU - Rombo L AD - Clinical Research Centre, Sormland County Council, Uppsala University, Uppsala, Sweden. FAU - Hedner, Jan AU - Hedner J AD - Pulmonary Medicine, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. FAU - Allen, Martin AU - Allen M AD - Department of Respiratory Medicine, Royal Stoke Hospital, University Hospitals of North Midlands, Stoke-on-Trent, UK. FAU - Walker, Paul P AU - Walker PP AD - Department of Respiratory Medicine, Aintree University Hospital, Liverpool, UK. FAU - De Ryck, Iris AU - De Ryck I AD - GSK, Siena, Italy. FAU - Tasciotti, Annaelisa AU - Tasciotti A AD - GSK, Siena, Italy. FAU - Casula, Daniela AU - Casula D AD - GSK, Siena, Italy. FAU - Moris, Philippe AU - Moris P AD - GSK, Rixensart, Belgium. FAU - Testa, Marco AU - Testa M AD - GSK, Siena, Italy. Electronic address: marco.x.testa@gsk.com. FAU - Arora, Ashwani K AU - Arora AK AD - GSK, Siena, Italy. LA - eng SI - ClinicalTrials.gov/NCT02075541 PT - Clinical Trial, Phase II PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190822 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Haemophilus Vaccines) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Female MH - Haemophilus Vaccines/*immunology/*therapeutic use MH - Haemophilus influenzae/*immunology/*pathogenicity MH - Humans MH - Immunity, Cellular/immunology MH - Immunity, Humoral/immunology MH - Male MH - Middle Aged MH - Pulmonary Disease, Chronic Obstructive/immunology/*prevention & control OTO - NOTNLM OT - COPD OT - Exacerbation OT - Immunogenicity OT - Non-typeable Haemophilus influenzae OT - Safety OT - Vaccine EDAT- 2019/08/27 06:00 MHDA- 2020/09/29 06:00 CRDT- 2019/08/27 06:00 PHST- 2019/03/29 00:00 [received] PHST- 2019/07/30 00:00 [revised] PHST- 2019/07/31 00:00 [accepted] PHST- 2019/08/27 06:00 [pubmed] PHST- 2020/09/29 06:00 [medline] PHST- 2019/08/27 06:00 [entrez] AID - S0264-410X(19)31021-7 [pii] AID - 10.1016/j.vaccine.2019.07.100 [doi] PST - ppublish SO - Vaccine. 2019 Sep 24;37(41):6102-6111. doi: 10.1016/j.vaccine.2019.07.100. Epub 2019 Aug 22.