Ten years of experience with the trivalent split-influenza vaccine, Fluarix (TM)

Background: The trivalent inactivated split-influenza vaccine, Fluarix(TM), has been available since 1992. Aim: To assess the safety and immunogenicity of the vaccine from studies in healthy adults and the elderly performed from 1992 to 2001 to comply with European Union registration requirements, and from studies in children and populations at high risk of severe influenza illness or influenza-related complications. Methods: Annual registration studies were performed in healthy adults aged 18-60 years and the elderly aged >60 years. Six studies in children aged 6 months- 18 years, and five studies in adults with high-risk conditions, were done during the same period. The high-risk populations included immunosuppressed patients with solid tumours or systemic malignancies, renal or liver transplant recipients, and patients with chronic obstructive pulmonary disease or insulin-dependent diabetes mellitus. Adults and children aged >36 months received 0.5ml of the vaccine by intramuscular or deep subcutaneous injection. Children aged 6-35 months received 0.25ml; in some children not previously vaccinated or exposed to influenza, a second dose was given 4 weeks later. Immunogenicity was determined by measuring haernagglutination inhibiting antibodies just before and 21 +/- 2 days after vaccination. Redness, swelling, induration and pain at the injection site were recorded, along with systemic symptoms such as fever. Results: In all registration studies (n = 1558), the vaccine consistently exceeded European Union immunogenicity criteria. Geometric mean titres in adults peaked 21 days after vaccination and remained above the protection level for all three strains for up to 12 months. In healthy adults and the elderly, seroprotection rates were 69-100% and consistently exceeded 82% from 1996. Immunogenicity in children (n = 364) and high-risk populations (n = 285) exceeded the targets for healthy adults. The vaccine was well tolerated in all age groups and populations. The most frequently reported symptoms in healthy adults and the elderly were local redness of >20mm (10-31%) and swelling of >20mm (11-16%). The incidence of fever >38.5degreesC was less than or equal to4% in healthy adults and high-risk groups; fever of >37degreesC was also rare (0-5%) in children over 6 years old, but was more frequent in younger children (11-27%). The reactogenicity of the vaccine was low in the high-risk populations. Conclusions: Fluarix(TM) has a good safety profile and is highly immunogenic in all age groups as well as in high-risk populations. The all-year persistence of antibodies means that the vaccine gives protection for the entire influenza season.