Monoclonal antibodies (mAbs) have great potential to counter biological warfare agents that are not addressed by currently available countermeasures. mAbs display exquisite specificity, are able to recruit host immune components to fight infection, confer near-immediate immunity once administered, can be successfully administered to all populations regardless of current immune status, and have a generally low rate of adverse reactions. The Industrialization Core's main responsibility will be to lead the translational research effort for the Viral Hemorrhagic Fever Immunotherapeutic Consortium (VHF-IC). The members of the Core have extensive experience with translating mAb research concepts into IND-enabling preclinical therapeutics for infectious diseases. The Core will make use of a rapid antibody manufacturing platform (RAMP) to provide well characterized, highly purified homogenous mAb preparations to facilitate direct comparisons between different mAbs by the individual Research Projects and Cores C and D. The Industrialization Core will be responsible for management of the advancement of products generated by the Research Projects through IND-enabling studies.
In Specific Aim 1, to quickly and economically address the supply needs for the Research Projects and Structure and Virology Cores, the Industrialization Core will produce all ofthe VHF-IC mAbs using the RAMP Nicotiana benthamlana manufacturing system. The Industrialization Core will ensure that all Research Projects and Cores C and D are using well-characterized mAbs with homogenous mammalian N-glycoforms that are produced and purified using a single protocol.
In Specific Aim 2, the Industrialization Core will be responsible for advancing the lead products selected from the three Research Projects by the Product Development Team through preclinical development.The Product Development Team will be responsible for prioritizing products and allocating Core resources appropriately and will work closely with the sponsoring companies (Mapp/Defyrus for filovirus products;Zaigen for arenavirus products) who will ultimately be responsible for developing the products after completion ofthe VHF-IC effort.
The filoviruses and arenaviruses are highly pathogenic viruses that cause rapidly progressing hemorrhagic fever. There are currently no FDA approved therapies or vaccines to treat infections with these viruses. The goal of this work is to develop therapeutic monoclonal antibodies that are effective against these deadly pathogens.
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