Effects of repeated vaccination and vaccine formulation on the induction of broadly neutralizing antibody responses against influenza A virus in children

The induction of broadly neutralizing antibodies (bNAbs) that target the hemagglutinin stalk domain is a promising strategy for the development of universal influenza virus vaccines. bNAbs can be boosted in adults by sequential exposure to heterosubtypic viruses through natural infection or vaccination. However, little is known about if/how bNAbs are induced by vaccination in more immunologically naive children. Here, we describe the impact of repeated seasonal influenza vaccination and vaccine type on induction of bNAbs in a well-characterized paediatric cohort enrolled in a series of randomized control trials of seasonal influenza vaccination. Repeated seasonal vaccination resulted in significant boosting of a durable bNAb response. Boosting of serological bNAbs titers was comparable within inactivated and live attenuated (LAIV) vaccinees and declined with age. These data provide new insights into vaccine-elicited bNAb induction in children, which has important implications for the design of universal influenza vaccine modalities in this critical population.