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The objective of this study was to compare the immunogenicity and safety of a single-dose regimen and a two-dose regimen of a trivalent virosome influenza vaccine (Inflexal Berna V) with those of a trivalent subunit influenza vaccine (Influvac) in children and adolescents with cystic fibrosis (CF). In an open, randomized, multicenter study with parallel groups, 11 young children with CF (1 to 6 years old) and 53 older children and adolescents with CF (>6 years old) were randomly assigned to one of the following immunization regimens: virosome vaccine at 0.5 ml on study day 0 or 0.25 ml on days 0 and 28 or a standard regimen of subunit vaccine, i.e., 0.5 ml on day 0 for older children and 0.25 ml on days 0 and 28 for younger children. Safety assessments, i.e., recording of systemic and local adverse events (AEs) and vital signs, were made for a 5-day observation period after each immunization. Hemagglutination inhibition (HI) titers were determined at baseline and 4 weeks after the single-dose and the two-dose immunizations, respectively. Immunogenicity was assessed according to the criteria of the European Agency for the Evaluation of Medicinal Products (EMEA). Both vaccines induced comparable HI antibody titers. Seroconversion (>4-fold rise in HI antibody titers, reaching a titer of >1:40) was achieved in 41 to 100% of the participants. Seroprotection (HI titer, >1:40) and a >2.5-fold increase in geometric mean titers were achieved in 100% of the participants. Thus, all three EMEA requirements for influenza vaccine efficacy were met by all treatment groups and for both vaccines. The virosome vaccine, when administered as a single dose, seemed to induce superior immunogenicity compared with the standard pediatric two-dose regimen. Totals of 42 and 57% of vaccinees receiving virosome and subunit vaccines, respectively, reported at least one local AE (predominantly pain). Totals of 84 and 71% of subjects receiving virosome and subunit vaccines, respectively, complained in response to questions of at least one systemic AE (mainly cough, fatigue, coryza, or headache). The majority of events were mild or moderate and lasted 1 or 2 days only. No obvious relationship was found between AE reporting rate and vaccine formulation, age group, or dose regimen. The relatively high AE reporting rate seemed to be partly related to the symptomatology of the underlying CF disease. In summary, the virosome and subunit vaccines induced in both age groups and against all three influenza strains an efficient immune response and were well tolerated by the children and adolescents with CF.

The long-term safety and immunogenicity of a polyvalent Pseudomonas aeruginosa conjugate vaccine was evaluated in 30 noncolonized cystic fibrosis patients. Four doses were administered over 3 years, and patients were followed for a mean of 38 months. No acute or long-term adverse effects were noted. Immunization engendered a significant antibody response to all vaccine components. A decline in titers during year 3 of observation was associated with a marked rise in the isolation of P. aeruginosa. This organism was isolated repeatedly from the respiratory tract of 4 patients and only once from 7 patients. The remaining patients were repeatedly culture-negative. Only 1 patient showed clinical deterioration associated with multiple isolations of P. aeruginosa.Pseudomonas aeruginosa is the leading cause of bronchopulmonary infection in patients with cystic fibrosis (CF) [1]. A substantial proportion of morbidity and mortality in this patient population is the result of recurrent pulmonary exacerbations subsequent to colonization. Rarely can P. aeruginosa be eradicated through antibiotic treatment. Further complicating treatment is the fact that multiply resistant strains often arise after repeated or prolonged drug therapy or prophylaxis.Colonization of the lower respiratory tract by mucoid variants of P. aeruginosa is preceded by infection of the upper respiratory tract by smooth strains [2]. Such natural exposure to P. aeruginosa stimulates a vigorous humoral antibody response to many somatic and extracellular antigens [3,4]. However, such antibodies do not prevent or even ameliorate subsequent infections. In fact, several laboratories [5,6] have noted a positive correlation between elevated anti-P aeruginosa antibody titers and a more severe disease course. This may be the result ofimmune complexes being deposited in the lungs and other organs.Anti-P. aeruginosa lipopolysaccharide (LPS) antibodies acquired after natural exposure are not effective at promoting opsonophagocytic killing [7]. We have found that anti-P. aeruginosa LPS antibodies acquired subsequent to colonization had very low average affinity constants, which These studies have been expanded to include 30 noncolonized patients followed for an average of38 months after vaccination. Various clinical. serologic, and bacteriologic parameters were analyzed. Materials and MethodsOver 31 months, 30 CF patients (13 males, 17 females) aged 1.6-24.0 years (mean, 8.3) were enrolled. All were in good health and clinically stable and had no history of infection with P. aeruginosa. On entry. sputum or throat swabs (or both) were negative for P. aeruginosa.Patients were immunized intramuscularly at O. 2, 12, and 36 months with a low (12.5 J.lg ofO-PS per serotype, n = 19) or a high (25 J.lg of O-PS per serotype, n = 11) dose of octavalent O-PS-toxin A conjugate vaccine [9] that contained the following International Antigen Typing System (IATS) LPS serotypes: 1.2/5.3.4,6,7. 10, and 16. Patients were observed for 60 min after immunization. For assessment of adverse r...