Comparison of immunogenicity and safety of a virosome influenza vaccine with those of a subunit influenza vaccine in pediatric patients with cystic fibrosis. Comparison of live and inactivated influenza vaccine in high risk children. Comparison of live attenuated and inactivated influenza vaccines in cystic fibrosis patients and their families: results of a 3-year study. Influenza immunization in children with cystic fibrosis.
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 (> or =4-fold rise in HI antibody titers, reaching a titer of > or =1:40) was achieved in 41 to 100% of the participants. Seroprotection (HI titer, > or =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. Bivalent, live attenuated intranasally administered influenza A vaccines were compared to inactivated, parenterally administered influenza A vaccines in a double-blind clinical trial in 55 children and young adults with cystic fibrosis. No qualitative or quantitative difference in symptomatology between the group receiving intranasal live vaccine versus placebo was observed. Serum immune responses to live vaccines were somewhat less than those to inactivated vaccine, particularly in adults. IgA response in nasal secretions was minimal in each vaccine group. In contrast, an IgG response in nasal secretions was commonly seen with both topically applied live vaccine and parenterally administered inactivated vaccine. Forty-one cystic fibrosis (CF) patients and 89 family members were immunized in a double-blind randomized 3-year trial with either intranasal live cold-adapted (ca) influenza A vaccine or the recommended intramuscular trivalent inactivated (triv) influenza vaccine. Local, respiratory, and systemic symptoms after vaccine were infrequent and did not differ between vaccine groups. CF patients did not differ from family members in immune response to either vaccine. Although antibody responses tended to be higher after triv vaccine, > or = 85% of subjects had mean hemagglutination inhibition antibody titers > or = 1:32 to influenza H1N1 and H3N2 after the first dose of either vaccine. Infection with influenza H3N2 viruses circulating during this study occurred with comparable low frequency in CF patients after ca (14 infections/100 subject-years of observation) or triv vaccine (10 infections/100 subject-years of observation). Influenza A ca vaccines appear to be safe, immunogenic alternatives to influenza A inactivated vaccines for CF patients and their families. Nineteen children with cystic fibrosis and aged between 5 and 13 years were randomized to receive two doses at monthly intervals of either a split-virion influenza vaccine (MFV-Ject, Institut Merieux) or a sub-unit vaccine (Fluvirin, Evans). In those completing the study, there was a satisfactory serological response. There was no statistically significant difference between the immunogenicity of the two vaccines as evaluated by haemagglutination inhibition or single radial haemolysis tests. The incidence of local side-effects was similar in the two groups.
There is currently no evidence from randomised studies that influenza vaccine given to people with cystic fibrosis is of benefit to them. There remains a need for a well-constructed clinical study, that assesses the effectiveness of influenza vaccination on important clinical outcome measures.