Efficacy of live attenuated influenza vaccine in children against influenza B viruses by lineage and antigenic similarity

Seasonal influenza vaccines, including live attenuated influenza vaccine (LAIV), contain three vaccine strains (two type A and one type B). Ideally, the hemagglutinin antigens of the recommended vaccine strains are antigenically similar to epidemic wild-type strains; in actuality, the antigenic match between circulating and vaccine strains each year can vary significantly owing to intermittent genetic reassortment and continuous antigenic drift. For influenza B, antigenic relatedness is further complicated by the existence of two distinct lineages. Consequently, the influenza B vaccine component can be of a completely different antigenic lineage from the circulating epidemic strains. Using data from nine randomized clinical trials in young children (6 months to 6 years of age), vaccine efficacy of LAIV against influenza B strains was assessed across this spectrum of antigenic relatedness. In an integrated analysis, vaccine efficacy of two doses of LAIV in vaccine-naive children was 86% against B strains of the same lineage and closely matched to the vaccine strain, 55% against strains of the same lineage but antigenically drifted from the vaccine strain, and 31% against strains of the opposite B lineage and antigenically unrelated to the vaccine strain. These data provide a more accurate assessment of the protection provided by the current trivalent vaccine and highlight the need for vaccination strategies that provide enhanced protection against both lineages of influenza B such as a quadrivalent influenza vaccine.