DNA Vaccine Technology to Rapidly Produce Cocktails of Polyclonal Antibodies to Neutralize Lethal Viruses of Military Importance

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.