PMID- 35509077 OWN - NLM STAT- MEDLINE DCOM- 20220506 LR - 20220716 IS - 1465-993X (Electronic) IS - 1465-9921 (Print) IS - 1465-9921 (Linking) VI - 23 IP - 1 DP - 2022 May 4 TI - Safety and immunogenicity of three doses of non-typeable Haemophilus influenzae-Moraxella catarrhalis (NTHi-Mcat) vaccine when administered according to two different schedules: a phase 2, randomised, observer-blind study. PG - 114 LID - 10.1186/s12931-022-02019-4 [doi] LID - 114 AB - BACKGROUND: Non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) infections are frequently associated with exacerbations of chronic obstructive pulmonary disease (COPD). Results were reported with a two-dose (0-2 months) schedule of an investigational AS01(E)-adjuvanted NTHi-Mcat vaccine containing three surface proteins from NTHi and one from Mcat. We evaluated the safety and immunogenicity of three NTHi-Mcat vaccine doses administered in two different schedules to adults with a smoking history (>/= 10 pack-years), immunologically representing the COPD population. METHODS: In this 18-month, randomised (1:1), observer-blind study with 6-month open follow-up, 200 healthy adults aged 40-80 years received NTHi-Mcat vaccine at 0-2-6 months and placebo at 12 months (0-2-6 group), or vaccine at 0-2-12 months and placebo at 6 months (0-2-12 group). Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days, respectively, post-vaccination, and potential immune-mediated diseases (pIMDs) and serious AEs (SAEs) throughout the study. Immune responses were assessed. RESULTS: No safety concerns were identified with the third vaccine dose or overall. Most solicited AEs were mild/moderate. Unsolicited AEs were reported in 16%, 16.1% and 14.4% of participants in the 0-2-6 group post-dose 1, 2 and 3, respectively, and 20%, 20.4% and 9.7%, respectively, in the 0-2-12 group. In 24 months, SAEs were reported in 12 participants in the 0-2-6 group and 9 in the 0-2-12 group (18 events in each group). There were three deaths (unknown cause, 0-2-6 group; myocardial infarction, lung cancer in 0-2-12 group). pIMDs were reported in three participants in the 0-2-6 group (non-serious inflammatory bowel disease, gout, psoriasis) and three in the 0-2-12 group (serious ulcerative colitis, two with non-serious gout). The SAEs, deaths and pIMDs were considered not causally related to vaccination. Antigen-specific antibody concentrations were higher at 12 months post-dose 1 with the 0-2-6 schedule than with the 0-2-12 schedule and at 12 months post-dose 3 were similar between schedules, remaining higher than baseline. CONCLUSIONS: No safety concerns were identified when the investigational NTHi-Mcat vaccine was administered via a 0-2-6 months or 0-2-12 months schedule to older adults with a smoking history. Persistent immune responses were observed after the third vaccine dose. Trial registration https://clinicaltrials.gov/ ; NCT03443427, registered February 23, 2018. CI - (c) 2022. GlaxoSmithKline Biologicals S.A. FAU - Galgani, Ilaria AU - Galgani I AD - GSK, Siena, Italy. ilaria.x.galgani@gsk.com. FAU - Annaratone, Margherita AU - Annaratone M AD - GSK, Siena, Italy. FAU - Casula, Daniela AU - Casula D AD - GSK, Siena, Italy. FAU - Di Maro, Gennaro AU - Di Maro G AD - GSK, Siena, Italy. FAU - Janssens, Michel AU - Janssens M AD - GSK, Rixensart, Belgium. FAU - Tasciotti, Annaelisa AU - Tasciotti A AD - GSK, Siena, Italy. FAU - Schwarz, Tino AU - Schwarz T AD - Institute of Laboratory Medicine and Vaccination Centre, Klinikum Wurzburg Mitte, Campus Juliusspital, Wurzburg, Germany. FAU - Ferguson, Murdo AU - Ferguson M AD - Colchester Research Group, Truro, Canada. FAU - Arora, Ashwani Kumar AU - Arora AK AD - GSK, Siena, Italy. LA - eng SI - ClinicalTrials.gov/NCT03443427 PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial DEP - 20220504 PL - England TA - Respir Res JT - Respiratory research JID - 101090633 RN - 0 (Vaccines) SB - IM MH - Aged MH - *Gout MH - Haemophilus influenzae MH - Humans MH - Moraxella catarrhalis MH - *Pulmonary Disease, Chronic Obstructive/prevention & control MH - *Vaccines PMC - PMC9069748 OTO - NOTNLM OT - COPD OT - Exacerbation OT - Immunogenicity OT - Moraxella catarrhalis OT - Non-typeable Haemophilus influenzae OT - Safety OT - Vaccination COIS- IG, MA, DC, GDM, MJ, AT, and AKA are employed by the GSK group of companies. IG holds shares in the GSK group of companies. DC declares two pending patents (unpublished) and AKA declares a published patent application 'Methods of Boosting the Immune Response'. TS has received honoraria for lecturing from the GSK group of companies, Pfizer, Bavarian Nordic, Janssen-Cilag, AstraZeneca and Sanofi and personal fees during the conduct of this study from the GSK group of companies, Pfizer, Biogen, Merck Serono, Biotest, Sequirus, Bavarian Nordic, and Sanofi. MF is employed by the Colchester Research Group which received payment from the GSK group of companies for the conduct of this study. The wife of MF is the owner of the Colchester Research Group. IG, MA, DC, GDM, MJ, AT, AKA, TS and MF declare no other financial and non-financial relationships and activities. EDAT- 2022/05/06 06:00 MHDA- 2022/05/07 06:00 PMCR- 2022/05/04 CRDT- 2022/05/05 00:09 PHST- 2021/10/12 00:00 [received] PHST- 2022/04/10 00:00 [accepted] PHST- 2022/05/05 00:09 [entrez] PHST- 2022/05/06 06:00 [pubmed] PHST- 2022/05/07 06:00 [medline] PHST- 2022/05/04 00:00 [pmc-release] AID - 10.1186/s12931-022-02019-4 [pii] AID - 2019 [pii] AID - 10.1186/s12931-022-02019-4 [doi] PST - epublish SO - Respir Res. 2022 May 4;23(1):114. doi: 10.1186/s12931-022-02019-4.