Successful vaccines work by inducing the development of memory B-cells that produce high-affinity antibody to antigens possessed by the microbe or virus against which the vaccine is directed. The key to the development of high-affinity antibodies is affinity maturation. In this process, somatic mutations are introduced into the genes that encode the antibody heavy and light chains. B-cells that bear mutated receptors with improved affinity for the eliciting ligand are thereby given a selective growth advantage and become the memory cells that provide protection against subsequent challenges. These events take place in the Darwinian microcosm of the germinal centers in the secondary lymphoid tissues. These structures self-organize via signals exchanged by T-cells, B-cells, follicular dendritic cells, and several kinds of stromal cells.
Daphne is a desktop application for modeling the immune response, with special focus on the spatiotemporal dynamics of the germinal center reaction and its modulation by candidate vaccine adjuvants. The software will comprise several core components: a modeling platform, a library of statistical analysis modules, a data management system, a data visualization system, a library of calibration data sets, and a graphical user interface. The software is being engineered for use by immunologists and other biomedical scientists eager to harness the power of modeling and computational biology but with little or no training in the mathematical sciences. These applications are being built around intuitive graphical user interfaces and extensive ontology-based run-time documentation. Behind the friendly exterior, however, is a powerful, flexible simulation engine directed initially at the study of the germinal center reaction, but capable of being utilized for the study of a wide variety of cellular systems. To download the latest installer, please refer to this link.
This work was supported by the Multiscale Systems Immunology (MSI) contract HHSN272201000053C and U19AI117892 grant under the Modeling Immunity for Biodefense program, which is funded by the NIH/NIAID.