Methods for antibody production
AssigneeSanofi Pasteur Vaxdesign Corporation
InventorsWilliam L. Warren, Robert Parkhill, Michael N. Nguyen, Guzman Sanchez-Schmitz, Heather Fahlenkamp, Russell Higbee, Donald Drake, III, Anatoly Kachurin, David Moe
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Abstract
The present invention relates to methods of constructing an integrated artificial immune system that comprises appropriate in vitro cellular and tissue constructs or their equivalents to mimic the normal tissues that interact with vaccines in mammals. The artificial immune system can be used to test the efficacy of vaccine candidates in vitro and thus, is useful to accelerate vaccine development and testing drug and chemical interactions with the immune system.
Claims34
A method for simultaneously producing a plurality of populations of antibodies having different binding specificities, the method comprising:
- (a) preparing a plurality of populations of dendritic cells, wherein each population of dendritic cells is matured in a separate culture in the presence of a different exogenous antigen, comprising adding peripheral blood mononuclear cells (PBMCs) to a plurality of separate vaccination site (VS) cultures, wherein the VS cultures are organized in a first multi-well format, wherein each of the VS cultures comprises a first substantially planar matrix, a plurality of cells consisting of endothelial cells and/or epithelial cells attached to the first matrix and an exogenous antigen of interest, wherein the exogenous antigen of interest differs between each VS culture, under conditions promoting maturation of dendritic cell precursors present in the population of PBMCs to dendritic cells;
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- (b) transferring each population of dendritic cells of (a) to separate three-dimensional artificial lymphoid tissue equivalent (LTE) cultures, wherein the LTE cultures are organized in a second multi-well format, wherein each of the LTE cultures comprises a second matrix and a plurality of lymphocytes attached to the second matrix, under conditions promoting production of antibodies by the lymphocytes, thereby simultaneously producing a plurality of populations of antibodies having different binding specificities.
Dependencies are inferred from the claim text.