Long-term immunogenicity and safety of a non-typeable - vaccine: 4-year follow-up of a phase 1 multicentre trial.

A multicomponent vaccine has been developed to reduce the frequency of acute exacerbations of COPD associated with non-typeable (NTHi) and (Mcat) infections, containing NTHi (PD and PE-PilA) and Mcat (UspA2) surface proteins. In a randomised, observer-blind, placebo-controlled study with two steps (NCT02547974), the investigational vaccine had good immunogenicity and no safety concerns were identified. In step 2, 90 adults aged 50-71 years with smoking history received two doses 60 days apart of one of two AS01-adjuvanted formulations containing 10 µg of each antigen (10-10-AS01) or 10 µg NTHi antigens and 3.3 µg UspA2 (10-3-AS01), or placebo. Long-term persistence of antigen-specific humoral antibodies was assessed in 81 participants during 3 years of follow-up after the initial 14-month study (NCT03201211). Antigen-specific antibody concentrations were measured in blood samples taken every 6 months. Safety monitoring evaluated serious adverse events (SAEs) and potential immune-mediated disease (pIMD). Immune responses against NTHi antigens persisted up to 4 years post-vaccination. For PD, PE and PilA, at each follow-up time point, adjusted antibody geometric mean concentrations (GMCs) were higher (non-overlapping 95% confidence intervals [CIs]) in the vaccine groups versus placebo and versus pre-vaccination. Antibody GMC point estimates were higher with 10-3-AS01 than with 10-10-AS01. For UspA2, 95% CIs included 1 for GMC ratios of 10-10-AS01 or 10-3-AS01 to placebo at each time point. During follow-up, SAEs were reported in nine (11.1%) participants, one of which was fatal (lung cancer, 607 days after second 10-10-AS01 dose). One non-serious pIMD, trigeminal neuralgia, was reported 771 days after second 10-3-AS01 dose. The SAEs and pIMD were considered not related to vaccination. Immune responses against NTHi antigens persisted for 4 years after two-dose vaccination with the investigational NTHi-Mcat vaccine. There was no persistent response against the Mcat antigen. No safety concerns were identified during the long-term follow-up.