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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19AI109762-01
Application #
8654212
Study Section
Special Emphasis Panel (ZAI1-LR-M (J1))
Project Start
2014-03-15
Project End
2019-02-28
Budget Start
2014-03-15
Budget End
2015-02-28
Support Year
1
Fiscal Year
2014
Total Cost
$1,193,970
Indirect Cost
$164,867
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Holtsberg, Frederick W; Shulenin, Sergey; Vu, Hong et al. (2016) Pan-ebolavirus and Pan-filovirus Mouse Monoclonal Antibodies: Protection against Ebola and Sudan Viruses. J Virol 90:266-78
Wec, Anna Z; Nyakatura, Elisabeth K; Herbert, Andrew S et al. (2016) A "Trojan horse" bispecific antibody strategy for broad protection against ebolaviruses. Science :
Pallesen, Jesper; Murin, Charles D; de Val, Natalia et al. (2016) Structures of Ebola virus GP and sGP in complex with therapeutic antibodies. Nat Microbiol 1:16128
Frei, Julia C; Nyakatura, Elisabeth K; Zak, Samantha E et al. (2016) Bispecific Antibody Affords Complete Post-Exposure Protection of Mice from Both Ebola (Zaire) and Sudan Viruses. Sci Rep 6:19193
Natesan, Mohan; Jensen, Stig M; Keasey, Sarah L et al. (2016) Human Survivors of Disease Outbreaks Caused by Ebola or Marburg Virus Exhibit Cross-Reactive and Long-Lived Antibody Responses. Clin Vaccine Immunol 23:717-24
Qiu, Xiangguo; Audet, Jonathan; Lv, Ming et al. (2016) Two-mAb cocktail protects macaques against the Makona variant of Ebola virus. Sci Transl Med 8:329ra33
Bornholdt, Zachary A; Turner, Hannah L; Murin, Charles D et al. (2016) Isolation of potent neutralizing antibodies from a survivor of the 2014 Ebola virus outbreak. Science 351:1078-83
Goba, Augustine; Khan, S Humarr; Fonnie, Mbalu et al. (2016) An Outbreak of Ebola Virus Disease in the Lassa Fever Zone. J Infect Dis 214:S110-S121
Robinson, James E; Hastie, Kathryn M; Cross, Robert W et al. (2016) Most neutralizing human monoclonal antibodies target novel epitopes requiring both Lassa virus glycoprotein subunits. Nat Commun 7:11544
Zeitlin, Larry; Whaley, Kevin J; Olinger, Gene G et al. (2016) Antibody therapeutics for Ebola virus disease. Curr Opin Virol 17:45-9

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