Construction of generic roadmaps for the strategic coordination of global research into infectious diseases of animals and zoonoses.

The Strategic Alliance for Research into Infectious Diseases of Animals and Zoonoses (STAR-IDAZ) International Research Consortium (IRC) coordinates global animal health research to accelerate delivery of disease control tools and strategies. With this vision, STAR-IDAZ IRC has constructed four generic research roadmaps for the development of candidate vaccines, diagnostic tests, therapeutics and control strategies for animal diseases. The roadmaps for vaccines, diagnostic tests and therapeutics lead towards a desired target product profile (TPP). These interactive roadmaps describe the building blocks and for each the key research questions, dependencies, challenges and possible solution routes to identify the basic research needed for translation to the TPP. The control strategies roadmap encompasses the vaccine, diagnostic tests, and therapeutic roadmaps within a wider framework focusing on the inter-dependence of multiple tools and knowledge to control diseases for the benefit of animal and human health. The roadmaps are now being completed for specific diseases and complemented by state-of-the-art information on relevant projects and publications to ensure that the necessary research gaps are addressed for selected priority diseases.

An Approach for a Synthetic CTL Vaccine Design against Zika Flavivirus Using Class I and Class II Epitopes Identified by Computer Modeling.

The threat posed by severe congenital abnormalities related to Zika virus (ZKV) infection during pregnancy has turned development of a ZKV vaccine into an emergency. Recent work suggests that the cytotoxic T lymphocyte (CTL) response to infection is an important defense mechanism in response to ZKV. Here, we develop the rationale and strategy for a new approach to developing cytotoxic T lymphocyte (CTL) vaccines for ZKV flavivirus infection. The proposed approach is based on recent studies using a protein structure computer model for HIV epitope selection designed to select epitopes for CTL attack optimized for viruses that exhibit antigenic drift. Because naturally processed and presented human ZKV T cell epitopes have not yet been described, we identified predicted class I peptide sequences on ZKV matching previously identified DNV (Dengue) class I epitopes and by using a Major Histocompatibility Complex (MHC) binding prediction tool. A subset of those met the criteria for optimal CD8+ attack based on physical chemistry parameters determined by analysis of the ZKV protein structure encoded in open source Protein Data File (PDB) format files. We also identified candidate ZKV epitopes predicted to bind promiscuously to multiple HLA class II molecules that could provide help to the CTL responses. This work suggests that a CTL vaccine for ZKV may be possible even if ZKV exhibits significant antigenic drift. We have previously described a microsphere-based CTL vaccine platform capable of eliciting an immune response for class I epitopes in mice and are currently working toward in vivo testing of class I and class II epitope delivery directed against ZKV epitopes using the same microsphere-based vaccine.