Figure 2.

Hypothetical protection patterns under different influenza A virus antigen exposure histories. (A) Initial natural infection with a group 2 hemagglutinin (HA) virus skews long-term protective responses toward epitopes present on the HA of that strain (epitopes 1–7, in shades of red). Subsequent infection with a group 1 virus results in weaker responses to that strain's epitopes (8–14, in shades of blue) because of diminished antigen levels and of competition between naive B cells reactive to the group 1 strain's epitopes and memory B cells reactive to the initial strain's epitopes. (B) Initial natural infection with a group 1 virus skews long-term protective responses toward group 1 epitopes. (C) Simultaneous delivery of group 1 and group 2 antigens during initial exposure, via live attenuated influenza vaccine (LAIV), allows for a broad immunological imprint and strong long-term protective responses against epitopes present on the HAs of both group 1 and group 2 viruses.