Rapid safety assessment of a seasonal intradermal trivalent influenza vaccine.

Seasonal influenza vaccine formulations must be updated annually to correspond to the influenza viruses in circulation. This was an uncontrolled, open-label, multi-center phase IV study conducted in Belgium to comply with interim European Medicines Agency (EMA) guidelines for rapidly evaluating the safety of newly formulated seasonal influenza vaccines. Adult volunteers received one dose of the 2014-2015 Northern Hemisphere formulation of licensed intradermal trivalent influenza vaccine at either the standard dose (9µg hemagglutinin/strain for 18-59 year-olds) or the high dose (15µg hemagglutinin/strain for ≥ 60 year-olds). Vaccinees recorded their solicited reactions and unsolicited adverse events for 7 d after vaccination. Solicited reaction frequencies were compared to historical reference values obtained from previous clinical trials to determine if the new formulations were excessively reactogenic or allergenic. A total of 210 participants (105 per age group) were included and vaccinated in October 2014. In both groups, pain, erythema, and pruritus were the most common solicited injection site reactions, and headache and myalgia were the most common solicited systemic reactions. Although the frequencies of shivering in 18-59 year-olds and malaise in ≥ 60 year-olds were higher than historical reference values, they were not considered indicative of excessive reactogenicity because almost all of these reactions were mild. The study design was endorsed by the EMA and permitted the reactogenicity of both vaccine formulations to be assessed within one month by collecting adverse events for 7 d. Both formulations exhibited acceptable safety profiles although this should be confirmed through forthcoming enhanced post-marketing safety surveillance systems.