The goal of this project is to develop and apply new technology for the delineation of polyclonal antibody specificities in sera from donors infected by or vaccinated against dengue viruses. The technology proposed here is built upon computational techniques for the generation and analysis of data related to monoclonal antibody and polyclonal serum interactions with the virus. Specifically, the technology will use large-scale antibody-virus neutralization matrices consisting of epitope-specific monoclonal antibody “neutralization fingerprints” (the potency-dependent pattern with which an antibody recognizes a set of diverse viral strains) to identify the types of antibodies present in a serum of interest. An analogous technology has been successfully applied to HIV-1 and should be generally extendible to other viruses, such as dengue, that exhibit sufficient levels of antigen sequence diversity. The polyclonal serum delineation approach described here has been a useful tool for efficient analysis of HIV-1 sera from infected and vaccinated individuals. Because of the substantial sequence diversity observed for dengue and the constantly increasing number of characterized monoclonal antibodies against this virus, we believe this fingerprinting-based approach should be extendible to dengue. Overall, the approach described here can be used for the analysis of sera both at the individual and population levels, and can thus be especially useful for high-throughput analysis of entire cohorts, such as for vaccine-elicited responses.
Conservation of dengue antibody epitopes on protein E. Maximum antibody-interactive area for each antigen residue is plotted as a heatmap (white-blue), capped at 100 Å2. Darker color corresponds to antigen residues that are a substantial part of at least one antibody epitope.
Primary: Ivelin Georgiev
Secondary: James E. Crowe, Jr.
Type of Trainee