Immunogenicity and Safety of 2 Dose Levels of a Thimerosal-Free Trivalent Seasonal Influenza Vaccine in Children Aged 6–35 Months: A Randomized, Controlled Trial

An estimated 5%–15% of the world's population experiences an influenza virus infection each year [1], with an estimated 90 million cases occurring in children [2]. Significant complications of influenza are most likely to occur in persons with underlying medical conditions, the elderly, and children, especially those aged <5 years [3, 4]. Children aged <3 years have the highest attack rates [5, 6], and otherwise healthy children aged <1 year have influenza-related hospitalization rates similar to high-risk adults [3]. Children are also efficient disseminators of influenza infection in households [7]. Although annual vaccination of infants and young children is recommended in many jurisdictions [8, 9], a limited number of studies have been conducted in this population, particularly in children aged 2 years in Canada, the United States, and, more recently, Europe. More data on the immunogenicity, efficacy, and safety of TIV in young children are needed. Various strategies have been used to improve influenza vaccine immune responses in young children, including use of adjuvants [14], administration via the intradermal instead of the intramuscular route [15], and use of different antigen doses, such as giving the adult dose [16] and doubling the adult dose [17]. Children in their first years of life do not benefit from the immunologic priming that results from multiple lifetime exposures to influenza infection or immunization, and consequently 2 influenza vaccine doses are recommended in the first year that younger children receive the vaccine [8]. Generally infants and toddlers are given half of the adult dose of influenza vaccines, a practice begun to avoid the reactogenicity associated with whole virus vaccines [18] that were evaluated >30 years ago. The dose of influenza antigen is known to play an important role in influenza vaccine immunogenicity, but little data are available on the relative safety and immunogenicity of a full (adult) dose (0.50 mL) compared with a half dose (0.25 mL) of TIV in children aged <3 years. In this study, the immunogenicity and safety of a preservative-free, prefilled syringe formulation of TIV (thimerosal-free TIV; TF-TIV) provided as the full adult dose of 0.50 mL compared with the usual children's dose of 0.25 mL were assessed in young children.