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 AS01E-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.
Keywords: AECOPD, acute exacerbations of chronic obstructive pulmonary disease; ANCOVA, analysis of covariance; AS01E, Adjuvant System AS01E, containing 3-O-desacyl-4′-monophosphoryl lipid A, QS-21 (Quillaja saponaria Molina, fraction 21) and liposome; Acute exacerbation; Antibody persistence; CI, confidence interval; COPD; COPD, chronic obstructive pulmonary disease; Clinical trial; ELISA, enzyme-linked immunosorbent assay; EU, enzyme-linked immunosorbent assay units; GMC, geometric mean concentration; GMR, geometric mean ratio; Haemophilus influenzae; LLOQ, lower limit of quantification; MPL, 3-O-desacyl-4′-monophosphoryl lipid A; Mcat, Moraxella catarrhalis; Moraxella catarrhalis; NTHi, non-typeable Haemophilus influenzae; PD, protein D; PE, protein E; PilA, Pilin A; QS-21, Quillaja saponaria Molina, fraction 21; SAE, serious adverse event; UspA2, ubiquitous surface protein A2; pIMD, potential immune-mediated disease.
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