There are no vaccines to prevent infections by Ebola virus, although it is among one of the most feared pathogens worldwide. The research proposed herein will advance development of vaccine candidates, with emphasis on technology that will create pilot lots of vaccine for preclinical testing and cost-saving scale-up capability using transgenic plants for safe production of strategic vaccine reserves. The proposed research exploits the facile capacity of plant cells to express and accumulate complex proteins that are not currently available via other expression systems. The research builds upon an ongoing funding investment by DoD directed to the creation of a """"""""cocktail"""""""" of monoclonal antibodies (MAbs) to use in post-exposure prophylaxis for Ebola virus infections; the DoD project utilizes transgenic plants because plant-derived MAbs can be rapidly expanded in commercial production without high-capital cost investments for traditional MAb production facilities. Recent research has shown that MAbs expressed in plant cells can be created as fusion molecules with antigenic protein domains as a C-terminal extension of the constant region of the antibody heavy chain. Highly immunogenic recombinant immune complexes (RICs) form when the variable region of the MAb recognizes the antigenic region of the fusion molecule. We will utilize three different MAbs to create RICs containing the sequences of the Ebola virus glycoprotein (GP) as well as GP fusions. Prototype vaccines will be produced in quantities sufficient for preclinical trials. Industrial participants of the application will develop purification technology for injected vaccines. An existing murine model will be utilized for immunogenicity and challenge trials, which will be followed by non-human primate vaccine evaluation of the lead vaccine candidates. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI061253-02
Application #
7032278
Study Section
Special Emphasis Panel (ZAI1-AR-M (M1))
Program Officer
Repik, Patricia M
Project Start
2005-03-15
Project End
2009-02-28
Budget Start
2006-03-01
Budget End
2007-02-28
Support Year
2
Fiscal Year
2006
Total Cost
$765,070
Indirect Cost
Name
Arizona State University-Tempe Campus
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
943360412
City
Tempe
State
AZ
Country
United States
Zip Code
85287
Phoolcharoen, Waranyoo; Bhoo, Seong H; Lai, Huafang et al. (2011) Expression of an immunogenic Ebola immune complex in Nicotiana benthamiana. Plant Biotechnol J 9:807-16
Phoolcharoen, Waranyoo; Dye, John M; Kilbourne, Jacquelyn et al. (2011) A nonreplicating subunit vaccine protects mice against lethal Ebola virus challenge. Proc Natl Acad Sci U S A 108:20695-700
Grantham, Michael L; Stewart, Shaun M; Lalime, Erin N et al. (2010) Tyrosines in the influenza A virus M2 protein cytoplasmic tail are critical for production of infectious virus particles. J Virol 84:8765-76
Huang, Zhong; Phoolcharoen, Waranyoo; Lai, Huafang et al. (2010) High-level rapid production of full-size monoclonal antibodies in plants by a single-vector DNA replicon system. Biotechnol Bioeng 106:9-17
Huang, Zhong; Chen, Qiang; Hjelm, Brooke et al. (2009) A DNA replicon system for rapid high-level production of virus-like particles in plants. Biotechnol Bioeng 103:706-14
Grantham, Michael L; Wu, Wai-Hong; Lalime, Erin N et al. (2009) Palmitoylation of the influenza A virus M2 protein is not required for virus replication in vitro but contributes to virus virulence. J Virol 83:8655-61