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

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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-022-02019-4.