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Abstract

Grant Number:	1R43AI052901-01A1
PI Name:	MORROW, PHILLIP R.
PI Email:	pmorrow@avanir.com
PI Title:
Project Title:	Diverse mix of Human MoAbs to treat Anthrax exposure

Abstract: DESCRIPTION (provided by the applicant): The long-term goal of this proposal (phase I and II) is the development of a human monoclonal antibody-based preparation for use in treating B. anthracis (anthrax) exposure or for use prophylactically. This preparation would most likely be composed of multiple, different monoclonal antibodies. Such a preparation would fill a significant void in the arsenal of reagents available to treat this biowarfare threat. Phase I specific aims are: 1) Evaluate the human antibody response of peripheral blood leukocytes from AVA vaccinated donors in the human lymphocyte engrafted SCID mouse (hu-PBL-SCID system). Immunogens will include a) recombinant Protective Antigen (PA), b) the active fragment of PA, c) Lethal Factor (LF), and (optionally) d) the Lethal Toxin formed from PA+LF. Antigen specific serum human antibodies will be detected by 'ELISA, and neutralizing antibody levels will be measured using the murine macrophage cell line RAW. 2) Evaluate Lethal Toxin treatment as an in vivo approach to select mice making neutralizing antibodies. 3) Generate, from selected animals, an initial series of human monoclonal antibodies specific for PA, and possibly LF. These will be characterized for neutralizing activity, and using BIACORE, affinity and epitope grouping. The main goal of the phase II proposal will be the configuration of at least one combination of human monoclonals which could be evaluated in vivo for the ability to protect and/or rescue from B. anthracis challenge. The phase II SBIR program may require the generation of a larger panel of antibodies, based on the success of phase I.

Thesaurus Terms:
Bacillus anthracis, anthrax, immunologic substance development /preparation, monoclonal antibody
antiantibody, antibody formation, antigen antibody reaction, bacterial antigen, bacterial toxin, leukocyte
SCID mouse, bioterrorism /chemical warfare, cell line, clinical research, enzyme linked immunosorbent assay, human tissue, neutralizing antibody, polymerase chain reaction, surface plasmon resonance

Institution:	AVANIR PHARMACEUTICALS
	11388 SORRENTO VALLEY RD, STE 200
	SAN DIEGO, CA 921211345
Fiscal Year:	2003
Department:
Project Start:	30-SEP-2003
Project End:	31-MAR-2004
ICD:	NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
IRG:	ZRG1

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