FluKB is a knowledge-based system focusing on data and analytical tools for influenza vaccine discovery. The main goal of FluKB is to provide access to curated influenza sequence and epitope data and enhance the analysis of influenza sequence diversity and the analysis of targets of immune responses. FluKB consists of more than 400,000 influenza protein sequences, known epitope data (357 verified T-cell epitopes, 685 HLA binders, and 16 naturally processed MHC ligands), and a collection of 28 influenza antibodies and their structurally defined B-cell epitopes. FluKB was built using a modular framework allowing the implementation of analytical workflows and includes standard search tools, such as keyword search and sequence similarity queries, as well as advanced tools for the analysis of sequence variability. The advanced analytical tools for vaccine discovery include visual mapping of T- and B-cell vaccine targets and assessment of neutralizing antibody coverage. FluKB supports the discovery of vaccine targets and the analysis of viral diversity and its implications for vaccine discovery as well as potential T-cell breadth and antibody cross neutralization involving multiple strains. FluKB is representation of a new generation of databases that integrates data, analytical tools, and analytical workflows that enable comprehensive analysis and automatic generation of analysis reports.