Cutting Edge: Rapid Boosting of Cross-Reactive Memory CD8 T Cells Broadens the Protective Capacity of the Flumist Vaccine

Memory CD8 T cells recognizing conserved proteins from influenza A virus (IAV), such as nucleoprotein, have the potential to provide protection in individuals who lack the proper neutralizing Abs. In this study, we show that the most potent CD8 T cell-inducing influenza vaccine on the market (Flumist) does not induce sufficient numbers of cross-reactive CD8 T cells to provide substantial protection against lethal nonhomologous IAV challenge. However, Flumist-primed CD8 T cells rapidly acquire memory characteristics and can respond to short-interval boosting to greatly enlarge the IAV-specific memory pool, which is sufficient to protect mice from nonhomologous IAV challenge. Thus, a current vaccine strategy, Flumist, may serve as a priming platform for the rapid induction of large numbers of memory CD8 T cells with the capacity for broad protection against influenza.