Specimens for histopathologic examination were collected in 10% neutral buffered formalin. The livers, spleens, kidneys, and brains obtained from infected mice and control animals were processed for histopathological and IHC examination as previously described [47] . Formalin-fixed and paraffin-embedded tissue sections were subjected to hematoxylin and eosin (H&E) by standard methods for evaluating histopathology and IHC staining for detecting RVFV antigens, respectively. For detecting RVFV antigens, the tissues were incubated with rabbit anti-N antibody [48] (1:500). Color was developed by using the fuchsin+ substratechromogen system (DAKO cytomation, Carpentaria, CA). Figure S1 Growth curve of rZH501-847-A and rZH501-847-A in MRC-5 cells. MRC-5 cells were inoculated with rZH501-847-A or rZH501-847-A at an moi of 0.02. Culture fluids were collected and virus titers were determined by a plaque assay that used VeroE6 cells. The results were obtained from three independent experiments.  Confronting Potential Influenza A (H5N1) Pandemic with Better Vaccines Influenza A (H5N1) viruses are strong candidates for causing the next influenza pandemic if they acquire the ability for efficient human-to-human transmission. A major public health goal is to make efficacious vaccines against these viruses by using novel approaches, including cell-culture system, reverse genetics, and adjuvant development. Important consideration for the strategy includes preparation of vaccines from a currently circulating strain to induce broad-spectrum immunity toward newly emerged human H5 strains. This strategy would be a good solution early in a pandemic until an antigenically matched and approved vaccine is produced. The concept of therapeutic vaccines (e.g., antidisease vaccine) directed at diminishing the cytokine storm frequently seen in subtype H5N1–infected persons is underscored. Better understanding of host–virus interaction is essential to identify tools to produce effective vaccines against influenza (H5N1). Infl uenza A (H5N1) viruses are strong candidates for causing the next infl uenza pandemic if they acquire the ability for effi cient human-to-human transmission. A major public health goal is to make effi cacious vaccines against these viruses by using novel approaches, including cell-culture system, reverse genetics, and adjuvant development. Important consideration for the strategy includes preparation of vaccines from a currently circulating strain to induce broad-spectrum immunity toward newly emerged human H5 strains. This strategy would be a good solution early in a pandemic until an antigenically matched and approved vaccine is produced. The concept of therapeutic vaccines (e.g., antidisease vaccine) directed at diminishing the cytokine storm frequently seen in subtype H5N1-infected persons is underscored. Better understanding of host-virus interaction is essential to identify tools to produce effective vaccines against infl uenza (H5N1).