Strong influenza-induced T FH generation requires CD4 effectors to recognize antigen locally and receive signals from continuing infection

This is the authors' abstract. We don't add key points for this paper.

Significance Influenza infection elicits strong, long-lived protective antibodies, but most current influenza vaccines give weaker, short-lived protection. We noted that live virus is still replicating, making antigen and causing inflammation at 7 d postinfection (dpi), while an inactivated vaccine provides antigen for at most 4 dpi. We show that the generation of key T follicular helper cells (T FH ) requires they recognize antigen locally at 6 dpi in the presence of ongoing viral infection. This creates a checkpoint that restricts T FH responses to dangerous infections that persist through the checkpoint. Using a live attenuated vaccine, akin to Flumist, we found that adding a second dose at 6 d generated a strong T FH response, suggesting an approach to improve vaccine strategies.