Abstract

Targeting immunogens to antigen presenting cells (APC) significantly enhances T cell activation and antibody production in vitro and in vivo, respectively, eliminating the need for traditional adjuvants. This proposal focuses on developing a biotin-binding Fcg receptor I (APC)-specific targeting element linked to a biotinylated functional element (tetanus toxin C- fragment). The ability of this anti-Fcg receptor I (FcgRI)-C-fragment conjugate to enhance T cell activation in vitro and in vivo will be demonstrated by monitoring T cell proliferation and cytokine production. The ability of this conjugate to enhance antibody production in vivo will be evaluated using human FcgRI transgenic mice which exhibit a cellular distribution and density of FcgRI similar to that in humans. Following immunization of transgenic mice with the anti-FcgRI-C-fragment conjugate, biodistribution of the conjugate, as well as antibody production to it, and its components will be monitored using radiolabeling and ELISA techniques, respectively. This two component approach to immune targeting promises to be safe, extremely versatile, and cost effective. In addition, it will facilitate the rapid evaluation and use of multiple targeting, antigen, and adjuvant combinations, significantly advancing, and possibly revolutionizing, current vaccine technology.

Proposed Commercial Applications

NOT AVAILABLE

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Business Technology Transfer (STTR) Grants - Phase I (R41)
Project #
1R41AI040442-01A2
Application #
2642824
Study Section
Special Emphasis Panel (ZRG2-SSS-4 (02))
Program Officer
Muszynski, Karen
Project Start
1998-07-01
Project End
2000-06-30
Budget Start
1998-07-01
Budget End
2000-06-30
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Medarex, Inc.
Department
Type
DUNS #
City
Princeton
State
NJ
Country
United States
Zip Code
08540