FluBub Study: Early influenza vaccination in infants

Young children, particularly those younger than six (6) months are at increased risk of severe influenza infection. Influenza vaccination is recommended for all children 6 months of age or older, but not for younger children. This is despite their risk of severe disease. The safety and immune response to previously available trivalent influenza vaccines (TIV; conferring protection against three influenza strains) has already been demonstrated in infants under 6 months of age, yet these reassuring data have not translated into routine use. There are no data on the safety and immune response in infants under 6 months of age to quadrivalent influenza vaccines (QIV; conferring protection against four strains; routinely used in Australia since 2016), nor is anything known about the impact of the now recommended maternal influenza vaccination on vaccine responses in infants under 6 months of age. We will conduct a phase 2, prospective randomised open-label feasibility study to assess both the safety of early (under 6 months) influenza vaccination in healthy young infants and its ability to generate a protective immune response via antibody production (immunogenicity). This will be compared with infants vaccinated according to the currently recommended schedule. Approximately 160 infants will be randomised to a vaccination strategy which will either have an early start to the schedule or commence according to the currently recommended schedule. Arm 1: Early vaccination and booster (receipt of QIV at 6 to <12 weeks; booster at least 4 weeks later); Arm 3: [Control] Standard vaccination (QIV at 6-7 months of age; booster at least 4 weeks later); Solicited and unsolicited adverse events will be monitored. Antibody responses will be assessed using the standard haemagglutination inhibition and focal reduction assays. The strength of immune responses will be assessed across the different arms, and impact of amount of maternal antibody present will be considered in the analyses. Additional testing using a systems serological approach will be performed on remaining samples to generate new knowledge on the mechanisms determining vaccine efficacy. Surveillance for influenza infection will occur during the influenza season with episodes of acute respiratory infection confirmed through nasopharyngeal samples. This is a pilot study that will tell us whether a larger, more informative study will be worthwhile.