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Live attenuated influenza vaccine (LAIV), or FluMist, was approved for use in the United States in 2003. This vaccine, administered intranasally, offers the advantage of stimulating immunity at the site of infection in the upper respiratory tract and, by mimicking natural infection, has the potential to elicit a multifaceted immune response. However, the development of immunity following LAIV administration requires viral replication, causing vaccine effectiveness to be impacted by both the replicative fitness of the attenuated viruses being administered and the degree of the host’s preexisting immunity. In this review, we discuss the current state of knowledge regarding the mechanisms of protection elicited by LAIV in children, contrast this with immune protection that develops upon vaccination with inactivated influenza vaccines, and briefly discuss both the potential advantages as well as challenges offered by this vaccination platform.

Understanding Immunity in Children Vaccinated With Live Attenuated Influenza Vaccine