FIG 1.

Generation of a model to study HA-specific heterosubtypic immunity in mice. (A) Recombinant B/Yamagata/16/88 viruses (B-HA viruses) expressing either wild-type B/Yamagata/16/88 HA or H1 (group 1) from A/PR/8/34 (B-H1; depicted in yellow) or H3 (group 2) from A/Panama/2007/99 (B-H3; depicted in orange). The genomic segments for expression of H1 and H3 via recombinant influenza B viruses include the packaging signals, transmembrane (TM-D) and endodomain (CT-D) derived from the influenza B virus HA (all depicted in blue) and the ectodomain from influenza A virus (depicted in orange). NCR, noncoding region. (B) Diagram of the study. Mice were sublethally infected with B-H1, B-H3, or wild-type influenza B virus, and at 90, 180, 270 or 360 days postpriming, mice were challenged with A/Vietnam/1203/04 H5N1 virus (PR8 reassortant, polybasic cleavage site deleted) at doses ranging from 10¹ to 10⁵ PFU/mouse. (C) Weight loss and survival kinetics were measured following H5N1 challenge. Antibody responses, including effector functions, were measured prechallenge and 21 days postchallenge (dpc).