We reviewed the evidence about the effect of vaccinating people with cystic fibrosis to prevent infection with Pseudomonas aeruginosa.
Cystic fibrosis is a hereditary disease where thick mucus is produced in the lungs. This can stop the lungs clearing bacteria such as Pseudomonas aeruginosa and other bacteria. This causes long-lasting lung infections in approximately 80% of adult patients; these infections result in permanent lung damage.
Vaccines have been developed which aim to reduce infection with Pseudomonas aeruginosa and it is important to know whether using these vaccines can prevent lung infection.
The evidence is current to: 30 March 2015.
We searched for vaccine trials where cystic fibrosis patients were selected at random to receive either an active vaccine or no vaccine (or a placebo, which is a dummy vaccine with no active medication). We also looked for trials comparing different types of vaccine or different schedules or doses of the same vaccine. We included three trials; two compared a Pseudomonas aeruginosa vaccine to a placebo and the third compared a vaccine to no vaccine. The two trials comparing a vaccine to placebo had 959 cystic fibrosis patients (483 in one and 476 in the other); the third trial recruited 37 patients with cystic fibrosis. The average age of the patients was about seven years in all three trials. All of the patients were free of infection with Pseudomonas aeruginosa at the start of the trials and had a lung function of at least 50% of predicted for age. The two large trials followed the patients for two and four years, respectively; the small trial followed the patients for between 10 and 12 years.
We were only able to present the results from one of the large trials (483 cystic fibrosis patients) comparing an active vaccine to a placebo and the small trial (37 cystic fibrosis patients) with a no vaccination comparison group. Results for the second large trial have not been published, but the manufacturers stated that results did not confirm the findings from an earlier trial and that further clinical development had been suspended. The results we have from the two trials show that after vaccination the risk of getting a chronic infection did not decrease and lung function was similar in both groups of cystic fibrosis patients. One of the patients from the large trial died during the two year follow-up period; in the small trial, one patient from each group had died after seven to eight years and by the end of the trial (10 to 12 years) six patients in each group had died. Those who died were all chronically infected with Pseudomonas aeruginosa. Investigators in the large trial, recorded 227 adverse events (four of which were classed as severe) in the vaccine group and 91 (one of which was classed as severe) in the placebo group. The large trial also reported a rise in antibodies against Pseudomonas aeruginosa with no change in the placebo group.
On the basis of these results, we cannot recommend the use of vaccines against Pseudomonas aeruginosa in patients with cystic fibrosis.
Quality of the evidence
We did have some concerns that in the large trial which provided data for this review, the participants in the vaccine group were apparently older, taller and heavier than those in the placebo group. This may be due to pure chance, but the paper did not acknowledge this fact. We also had some concerns about how the cystic fibrosis patients in the small trial were randomised to the different treatments.
Vaccines against Pseudomonas aeruginosa cannot be recommended.
Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed. This is an update of a previously published review.
To assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis.
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search 30 March 2015). We previously searched PubMed using the terms vaccin* AND cystic fibrosis (last search 30 May 2013).
Randomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in cystic fibrosis.
The authors independently selected trials, assessed them and extracted data.
Six trials were identified. Two trials were excluded since they were not randomised and one old, small trial because it was not possible to assess whether is was randomised. The three included trials comprised 483, 476 and 37 patients, respectively. No data have been published from one of the large trials, but the company stated in a press release that the trial failed to confirm the results from an earlier study and that further clinical development was suspended. In the other large trial, relative risk for chronic infection was 0.91 (95% confidence interval 0.55 to 1.49), and in the small trial, the risk was also close to one. In the large trial, one patient was reported to have died in the observation period. In that trial, 227 adverse events (4 severe) were registered in the vaccine group and 91 (1 severe) in the control group. In this large trial of a vaccine developed against flagella antigens, antibody titres against the epitopes contained in the vaccine were higher in the vaccine group compared to the placebo group (P < 0.0001).