Members of the Flagella Vaccine Trial Study Group in Germany enrolled 483 patients with cystic fibrosis (CF) from 24 European CF centers into a randomized, double-blind, placebo-controlled trial of a bivalent Pseudomonas aeruginosa vaccine. Patients two to 18 years of age and free of P aeruginosa colonization as determined by serum antibody titers and throat swab culture were randomized to vaccine (n=239) or placebo (n=244). The groups were not significantly different with regard to sex, age, body mass index, or FEV1. Intramuscular injections were given monthly for three months, followed by a booster at one year. Only 381 patients completed the full protocol of four vaccinations, and a subanalysis was performed on this group. Primary outcome measures included frequency of P aeruginosa infection/colonization as determined by throat cultures and serum antibody titers (other than flagella antibodies) and the frequency of chronic infection as defined by three positive throat swabs and/or three positive serum antibody titers against P aeruginosa antigens. Analysis of patients completing the protocol (n=381) revealed that during the two-year period of the study, 19.6% (37/189) of patients in the vaccine group and 30.7% (59/192) in the placebo group developed colonization or infection with P aeruginosa (P=.02). Chronic infection developed in 3.2% of vaccinated patients and 6.3% of the placebo patients (not statistically significant).
The vaccine series resulted in a high concentration of flagella-specific serum IgG antibodies. However, the majority of patients with positive P aeruginosa isolates were infected with strains that exhibited a flagella type not included in the vaccine antigens. There was no difference between the groups with regard to rate of decline in FEV1 during the study period. Vaccination was well tolerated; while adverse events were more common in the vaccine group (227 vs 91), these reactions were generally mild and resembled those associated with other childhood immunizations.
The authors conclude that active immunization with bivalent P aeruginosa flagella vaccine protects some, but not all, patients with CF against an initial episode of P aeruginosa infection, and suggest that any delay in the onset of chronic infection with P aeruginosa should result in longer survival.
Drs. Dubik and Barton have disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.
Affecting about 80,000 people worldwide, including 30,000 in the US, CF is the most common life-shortening inherited disease among Caucasians, with a median survival of approximately 33 years.1,P aeruginosa is the most frequently described opportunistic pathogen and a leading cause of morbidity and mortality in CF patients.2 The median age at first P aeruginosa infection is 12 months, but with aggressive antibiotic therapy chronic infection can be delayed until the teen years. Approximately 80% of CF patients eventually become infected with P...