SBIR-STTR Award

In this Phase I STTR proposal we will determine the ruggedness of the genetic immunization technique in the production of duck egg derived immunoglobulin; specifically the natural F(ab?)2 analog, IgY^Fc. We have already demonstrated that potently neutralizing duck egg antibodies generated with an early candidate Andes virus DNA vaccine, delivered via intramuscular electroporation, can protect after lethal challenge. We now seek to optimize the elements necessary to deploy a commercially viable platform system for the rapid production of passive immunity products as countermeasures to emerging viral threats. Mammalian or avian (Mallard duck) codon optimized Andes virus DNA vaccine variants of the original will be administered to ducks utilizing electroporation or a needle-free device. An increased potency and/or response frequency along with a decreased response time would represent a significant and enabling progression in the field. The work will be coupled with a small parallel study in sheep with Andes and Junin virus DNA vaccine candidates. Endpoints as measures of success will be determined by known correlates of protection using plaque reduction neutralizing tests and pseudoviral assays. Simple reactogenicity studies will also be performed with all full-length and despeciated immunoglobulin?s and the results compared to licensed polyclonal and monoclonal products.

Keywords:
Dna Vaccine, Polyclonal Antibodies, Viral Hemorrhagic Fever, Andes Virus, Postexposure

In this Phase II STTR proposal we will demonstrate the scalability and ruggedness of the production system necessary for the commercialization of the goose egg-derived immunoglobulin product that is a countermeasure to the lethal (40 %) Hantavirus Pulmonary Syndrome caused by Andes Virus (ANDV). A major objective will be creating a Quality System (QS) around the global process that aligns it with standards commensurate with FDA guidance. Related objectives will be the development of critical assays and the harmonization of the related Standard Operating Procedures into the QS. Pharmacokinetic and repeat dose studies will be performed that will allow us to better evaluate the quantities to be used and routes of delivery for the anti-ANDV product in the challenge study. Endpoints as measures of success would be the reproducible production of 5 g lots of low impurity anti-ANDV and the use of such lots affording clinically significant protection up to five days after challenge. These results would indicate the commercial viability of a platform that is based on the use of genetic immunization in geese as a means of creating therapies for Category-A pathogens for which no countermeasures or vaccines exist.

Keywords:
DNA vaccine, polyclonal antibodies, viral hemorrhagic fever, Andes Virus, postexposure