Lectin-Antigen Conjugates as a Vaccine Delivery System

The induction of protective immunity against many intracellular parasites is triggered followingexposure to living organisms that retain the ability to infect host cells. This requirement for intracellularreplication appears necessary for processing and presentation of relevant parasite antigens by theendogenous antigen processing pathway. Antigens processed through this pathway become associatedwith MHC Class I molecules and thus become appropriate configurations that activate T lymphocytesof the CD8+ T-cell subset. We will evaluate an alternative in the use of viable organisms for deliveryof antigen for vaccination purposes. The investigator will evaluate Lectin-Antigen complexes as anantigen-delivery strategy for placing antigen into the cytoplasmic domain for processing and presentationto T cells. This Phase I feasibility study will use the lectin, ricin B chain, which will act as a deliveryvehicle of a model antigen, listeriolysin O from Listeria monocytogenes. Listeriolysin O (LLO) will becovalently linked to the ricin B chain to form a complex that will bind to membrane-associatedgalactose-containing glycoproteins. Binding of the glycoprotein by the ricin B chain-LLO complex ispredicted to stimulate internalization of the complex and processing of internalized proteins. The studymay 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 thisPhase I study is the first step in the development of an antigen delivery system for vaccination againstan array of intracellular pathogens. The long term focus of this project will be the development of novelcarrier reagents recombined with purified or genetically engineered protein antigens that have beenproposed as targets of protective cell-mediated immunity.