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
Saphire, Erica Ollmann; Schendel, Sharon L; Fusco, Marnie L et al. (2018) Systematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Protection. Cell 174:938-952.e13
Siragam, Vinayakumar; Wong, Gary; Qiu, Xiang-Guo (2018) Animal models for filovirus infections. Zool Res 39:15-24
West, Brandyn R; Moyer, Crystal L; King, Liam B et al. (2018) Structural Basis of Pan-Ebolavirus Neutralization by a Human Antibody against a Conserved, yet Cryptic Epitope. MBio 9:
Gilchuk, Pavlo; Mire, Chad E; Geisbert, Joan B et al. (2018) Efficacy of Human Monoclonal Antibody Monotherapy Against Bundibugyo Virus Infection in Nonhuman Primates. J Infect Dis 218:S565-S573
Yang, Shu; Xu, Miao; Lee, Emily M et al. (2018) Emetine inhibits Zika and Ebola virus infections through two molecular mechanisms: inhibiting viral replication and decreasing viral entry. Cell Discov 4:31
Gilchuk, Pavlo; Kuzmina, Natalia; Ilinykh, Philipp A et al. (2018) Multifunctional Pan-ebolavirus Antibody Recognizes a Site of Broad Vulnerability on the Ebolavirus Glycoprotein. Immunity 49:363-374.e10
Nyakatura, Elisabeth K; Zak, Samantha E; Wec, Anna Z et al. (2018) Design and evaluation of bi- and trispecific antibodies targeting multiple filovirus glycoproteins. J Biol Chem 293:6201-6211
Zhu, Wenjun; Zhang, Zirui; He, Shihua et al. (2018) Successful treatment of Marburg virus with orally administrated T-705 (Favipiravir) in a mouse model. Antiviral Res 151:39-49
Wong, Gary; Mendoza, Emelissa J; Plummer, Francis A et al. (2018) From bench to almost bedside: the long road to a licensed Ebola virus vaccine. Expert Opin Biol Ther 18:159-173
Wong, Gary; Qiu, Xiangguo (2018) Funding vaccines for emerging infectious diseases. Hum Vaccin Immunother 14:1760-1762

Showing the most recent 10 out of 62 publications