SBIR-STTR Award

Flow Pharma, Inc. is a biotechnology company in the San Francisco Bay Area developing fully synthetic cytotoxic T lymphocyte (CTL)stimulating peptide vaccines for Marburg virus. The FlowVax vaccine platform allows us to create dry powder formulations of biodegradablemicrospheres and TLR adjuvants incorporating class I and class II T cell epitopes. FlowVax vaccines can be designed for delivery by injection orinhalation. An open source computer model originally developed by Microsoft Research and enhanced by us with Artificial Intelligence deeplearning, allows us to select optimal class I epitope targets on viruses for CTL attack. We will use this computer model to select class I peptidesto Marburg proteins. We will then design complimentary class II peptides for the class I peptides using the TEPITOPE and ProPred algorithms.The La Jolla Institute for Allergy & Immunology will determine the MHC binding affinity of the selected class I and class II epitope candidatesfor selected Mamu and HLA specificities using purified MHC molecules and high affinity radiolabeled peptide ligands. High affinity cross-reactiveclass I and II peptides will be selected as vaccine candidates to protect Rhesus Macaques from a lethal challenge of Marburg virus with crossprotectivepeptides to protect humans.

Through this STTR contract, we propose to evaluate the efficacy of our vaccine, FlowVax Marburg, in nonhuman primates (NHPs). This will be achieved through four Tasks. In Task 1, we will manufacture the vaccine in a quantity sufficient for the animal studies. In Task 2, we will perform MHC genotyping on a representative population of NHPs and, based on results, select a set of MHC-matched NHPs for ensuing dose escalation and challenge studies. In Task 3, we will perform a dose escalation study in NHPs via direct lymph node immunization followed by aerosol challenge to a lethal dose of Marburg virus in order to assess efficacy. Finally, in Task 4, we will perform a dose escalation study in NHPs via intranasal immunization followed by aerosol challenge to a lethal dose of MARV in order to assess vaccine efficacy through this alternative mode of administration. This will allow us to compare the efficacy of FlowVax Marburg delivered by direct lymph node injection (Task 3) to intranasal delivery (representing a more practical method of vaccine delivery in humans).