Comparison of Immunogenicity and Safety of a Virosome Influenza Vaccine with Those of a Subunit Influenza Vaccine in Pediatric Patients with Cystic Fibrosis

Abstract

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.

Vaccinating High-Risk Children with the Intranasal Live-Attenuated Influenza Vaccine: the Quebec Experience

“…In our cohort of participants, 64% (107/168) experienced and reported at least one solicited AEFI in the first week following vaccination, which is similar to proportions reported after IIV: 15/ 21 (71%) participants with CF vaccinated with IIV reported at least one systemic AEFI in the 5 days following vaccination [41]. Fiftynine (35%) patients had onset of fever during the first six days following vaccination with most febrile children observed on day 4 post-vaccination (n = 42, 25%).…”

Immunisation in the current management of cystic fibrosis patients

“…The immunogenic effect of influenza vaccines in CF children is comparable to that of healthy individuals [67] and several studies have demonstrated the safety of influenza vaccinations in children with CF [68]. One study has compared a virosome adjuvant vaccine with a subunit vaccine in paediatric CF patients detailing their strong efficacy and tolerability [69]. The coming live attenuated intranasal vaccines will offer an alternative more suitable for children and reduce the number of injections.…”

Humoral and Cellular Response to Influenza Vaccine in HIV-Infected Children With Full Viroimmunologic Response to Antiretroviral Therapy

“…Recently, a virosomal-adjuvanted subunit influenza vaccine was shown to be well tolerated and endowed with improved immunogenicity. [36][37][38][39][40] To evaluate the amplitude and duration of the cellmediated and humoral immune responses elicited by such vaccine preparation in pediatric HIV infection, we designed a study protocol enrolling HIV-infected children in whom long-term HAART resulted in an optimal immunovirologic response to therapy.…”