Long-term immunogenicity and safety of a non-typeable Haemophilus influenzae-Moraxella catarrhalis 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 Haemophilus influenzae (NTHi) and Moraxella catarrhalis (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(E)-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.