Fig 1.

Vaccination with cHA elicits broad-based immunity that mediates protection from heterologous and heterosubtypic virus challenges. Animals were electroporated with DNA encoding cH9/1 and then were vaccinated with cH6/1 (replaced by H1 for panel F) and boosted with cH5/1 (replaced by H1 for E) soluble proteins (purple triangles; n = 10) or BSA (black triangles; n = 5), while positive-control mice received inactivated virus vaccine intramuscularly (pink squares; n = 5). (A) Schematics of vaccination and challenge. Purple, H1 stalk; green, H9 head; blue; H6 head; red, H5 head. The conserved stalk of the challenge viruses is indicated in purple, whereas the generic head domain is shown in gray. (A) Animals were vaccinated and then challenged with pH1N1, H1N1, H5N1, and H6N1 viruses. (B) Mice were challenged with pH1N1 virus and weighed daily. (C) Kaplan-Meier curve depicting survival. (D to G) Kaplan-Meier curves depicting survival upon viral challenge with the FM1 (H1N1) (D), PR8 (H1N1) (E), H5N1 (F), and H6N1 (G) strains. Survival of the chimeric HA vaccine group over that of the cH9/1 DNA-plus-BSA control group was highly significant for all viral challenges (P < 0.0001 for pH1N1, PR8, and H5N1 viruses, P = 0.0007 for FM1, and P = 0.0002 for H6N1 virus). (H) Mice that were vaccinated in a similar manner to that presented in panel A were not protected against challenge with an H3N2 virus strain.