Recently, a team of researchers from the Nordic Cochrane Centre (NCC) an independent research center that is part of The Cochrane Collaboration, an international network of individuals and institutions committed to preparing, maintaining, and disseminating systematic reviews of the effects of health care, released recommendations against the use of Pseudomonas aeruginosa (P. aeruginosa) vaccines in patients with cystic fibrosis (CF). The study, entitled “Vaccines for preventing infection with Pseudomonas aeruginosa in cystic fibrosis” was published in the latest edition of the Cochrane Library.

CF is a chronically progressive life-threatening disease caused by a genetic mutation that disrupts the body’s ability to hydrate and effectively clear mucus in the lungs and/or digestive tract. According to the CDC, in the US, approximately 1,000 new cases are diagnosed each year with more than 75% of those patients under the age of two. An estimated 30,000 children and adults in the US and 70,000 worldwide have the disease. Patients diagnosed with CF have a lifespan of approximately 30 years, with many patients living into their forties.

The genetic mutation that causes CF affects the normal functioning of the lungs and digestive system by creating abnormal amounts of very sticky mucus that covers the lungs, pancreas, and other important organs of the respiratory and digestive systems. This sticky mucus attracts foreign pathogens, such as viruses and bacteria, making patients more susceptible to infectious diseases (i.e. P. aeruginosa). The high microbial burden causes inflammation of the lung tissue and a high likelihood of tissue destruction due to the frequency of infections.

About the Study:

The researchers conducted the systematic review by first searching for the following clinical trials:

• Vaccine trials where CF 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).
• Vaccine trials comparing different types of vaccine or different schedules or doses of the same vaccine.

The review resulted in 3 trials that met the investigative criteria, including:

1. Two trials comparing a P. aeruginosa vaccine to a placebo in 959 CF patients.
2. A trial comparing a vaccine to no vaccine in 37 CF patients.

The review resulted in patients with an average age of 7 years old, with all of the patients free of infection with P. aeruginosa at the start of the trials and having a lung function of at least 50% of their predicted age.  These patients were followed from between 2 and 12 years and the following clinical outcomes were observed:

• 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.
• Patients who died were all chronically infected with P. aeruginosa
• There were 227 adverse events recorded by the investigators (four of which were classed as severe) in the vaccine group and 91 (one of which was classed as severe) in the placebo group.
• There were 91 adverse events recorded by the investigators (one of which were classed as severe) in the placebo group
• There was a rise in antibodies against P. aeruginosa with no change in the placebo group.

When discussing the results of the study, the investigators wrote, “The trial data we reviewed did not suggest that the vaccines tested for preventing infection against P. aeruginosa were effective. Effective vaccines have been developed against other bacteria, e.g. Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae, and there is clearly a need for additional basic research to further increase our understanding of those elements of the immune response to P. aeruginosa that could potentially have a protective effect in patients with CF. Beneficial alterations in immune responses have been seen in animal experiments (Johansen 1995) and should be further evaluated (Moser 2000).”