Research Project
8782396
DESCRIPTION (provided by applicant): For many years, the use of protein and peptide antigens to induce specific immune responses has been an area of intense effort with the goal of developing improved vaccines. In principle, this approach is attractive because it has the potential to provide immunological specificity, tighter control of manufacturing processes, and elimination of most of the secondary sources of materials or contaminants associated with the production of the immunogen. However, proteins and peptides are typically ineffective at stimulating host immune responses when used as soluble antigens. Co-administration with immunostimulatory adjuvant molecules (IAMs) can significantly improve the immune response against protein and peptide antigens, but differences in their physicochemical properties often makes their delivery together to the cells of the immune system inefficient. Since protein and peptide antigens generally require administration with a strong adjuvant to induce potent immune responses, in particular, cytotoxic T cell responses, if the target antigen can be packaged together with an IAM in a particulate delivery vehicle, a much more effective immunogen could be created. To overcome the problem of combining protein and peptide antigens together with a potent adjuvant molecule, we have been developing a nanoparticulate liposome-based technology, called the VesiVax (r) system, to facilitate the vaccine development process. In these studies, we propose to demonstrate that VesiVax(r) formulations of cyclic dinucleotides (CDNs) can stimulate potent immune responses. The VesiVax(r) CDN formulation to be created through this proposal will be designed to be scalable to commercial quantities and cost effective to manufacture. In the SBIR Phase I studies, we will first formulate different concentration of a CDN analog in the VesiVax(r) system. To evaluate the immune response and efficacy of the VesiVax(r) CDN formulations, the liposomes will be formulated with our well-characterized antigen that is based on the gD ectodomain glycoprotein (gD1-306-HD) of the herpes simplex virus type 2 (HSV2). VesiVax(r) CDN formulations containing gD1-306-HD will be prepared and evaluated in female mouse and guinea pig models of HSV2 infection.
