Reduction of COPD severe acute exacerbations by candidate vaccine

The presented study was the first randomised, multicentre, placebo-controlled, observer-blind, phase 2b trial to investigate a candidate vaccine against two commonly detected bacteria in COPD patients. While the study failed to meet the primary endpoint of reducing moderate and severe acute exacerbations, a significant reduction of 37% was found for severe acute exacerbations in COPD.

COPD is a leading cause of death worldwide. An increase of 17.5% was seen in deaths in 2017 compared with 2007. Despite progress in the vaccination field, a vaccine against the most frequently detected bacteria associated with acute exacerbation in COPD patients has not been licensed yet. Acute exacerbations in COPD are heterogenous in nature. Bacterial infections with non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) are frequently associated with acute exacerbations. Prof. Stefan Andreas (Gastarzt Abteilung Pneumologie der Medizinischen Klinik II Gießen, Germany) and his team have been investigating a candidate NTHi-Mcat vaccine containing bacterial surface proteins [1].

The aim of the current randomised, placebo-controlled, observer-blind, multicentre trial was to investigate whether vaccination reduces the number of exacerbations in patients with COPD. In the trial, 67 sites were recruiting patients, mainly in Europe but also in the United Kingdom and the United States. The most important inclusion criterium was having at least 1 moderate or severe acute exacerbation of COPD in the last 12 months. Patients were randomised to receive placebo or the vaccine containing NTHi and Mcat antigens combined with a liposome-based adjuvant, added to create a stronger immune response. Two intermuscular injections of vaccine or placebo were given 60 days apart. Sputum and blood samples were collected for immunogenicity assessment. Quantitative PCR was done to detect bacteria in sputum. The primary outcome of the study was the rate of moderate or severe exacerbations 1 year after the vaccination period, starting 1 month after the 2-dose vaccination.

In total, 673 COPD patients were included in the study: 340 patients in the vaccine group and 333 patients in the placebo group. No vaccine efficacy was shown for moderate and severe acute exacerbations of COPD, mild acute exacerbations of COPD, and moderate acute exacerbations of COPD (P=0.83, P=0.76, P=0.37, respectively; see Figure 1). However, severe acute exacerbations of COPD (n=38 vaccine group; n=59 control group) were reduced by 36.7% (P=0.07).

Figure 1: Vaccine efficacy data [1]



No safety concerns were identified. Only a small number of severe adverse events and no vaccine-related serious adverse events were reported. Local adverse events as mild pain, redness and/or swelling at the injection side were common. Immunogenicity results showed that the candidate vaccine induced an antigen-specific immune response (see Figure 2).

Figure 2: Vaccine immunogenicity data [1]



Taken together, the primary endpoint of reducing the frequency of moderate and severe acute exacerbations of COPD was not met. However, immunogenicity and vaccine efficacy data looked promising as a reduction of severe acute exacerbations of COPD was demonstrated. The presented study was the first randomised controlled trial to investigate a vaccine against two frequently detected bacteria in COPD patients. The data may encourage further investigation of the candidate NTHi-Mcat vaccine.

1. Andreas S, et al. Late Breaking Abstract - First-time assessment of efficacy of candidate vaccine to prevent acute exacerbations of chronic obstructive pulmonary disease (AECOPD): multicentre, randomised, controlled, observer-blind phase 2b trial. Abstract 210. ERS 2021, 5–8 September.

 

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Posted on 9 November, 2021