Research Project
2070938
DESCRIPTION: (Adapted from investigator's abstract) The induction of protective immunity against many intracellular parasites is triggered following exposure to living organisms that retain the ability to infect host cells. This requirement for intracellular replication appears necessary for processing and presentation of relevant parasite antigens by the endogenous antigen processing pathway. Antigens processed through this pathway become associated with MHC Class I molecules and thus become appropriate configurations that activate T lymphocytes of the CD8+ T-cell subset. This proposal will evaluate an alternative to the use of viable organisms for delivery of antigen for vaccination purposes. The investigator will evaluate Lectin-Antigen complexes as an antigen- delivery strategy for placing antigen into the cytoplasmic domain for processing and presentation to T cells.This Phase I feasibility study will use the lectin, ricin B chain, which will act as a delivery vehicle of a model antigen, listeriolysin O from Listeria monocytogenes. Listeriolysin O (LLO) will be covalently linked to the ricin B chain to form a complex that will bind to membrane-associated galactose- containing glycoproteins. Binding of the glycoprotein by the ricin B chain-LLO complex is predicted to stimulate internalization of the complex and processing of internalized proteins. The study may determine if LLO is then processed and presented in a form that is recognized by CD8+ Listeria-immune lymphocytes. The information derived from the experiments completed during this Phase I study is the first step in the development of an antigen delivery system for vaccination against an array of intracellular pathogens. The long term focus of this project will be the development of novel carrier reagents recombined with purified or genetically engineered protein antigens that have been proposed as targets of protective cell-mediated immunity.
