NSG-hu mice generate HIV specific human immune responses after gp96 vaccination (46.14)

Abstract

Abstract NOD.SCID common gamma chain (NSG) knockout mice have no functional adaptive immune system of their own; they readily accept human CD34+ hematopoietic stem cell xenografts (NSG-hu). Therefore, NSG-hu mice present a model system in which to study human immunology. Previously, we developed a cell based vaccine combining secreted heat shock protein gp96 and HIV gag protein (293-gp96Ig-HIVgag). Here we use NSG-hu mice vaccinated with 293-gp96Ig-HIVgag to study human immunological responses. Flow cytometry analysis of peripheral blood in pre-vaccination (8-9 week old) animals revealed human engraftment (mCD45 vs. hCD45) ranging from 25%-50%. In addition, human CD45+ cells were detected in specific tissues (spleen, PEC, IEL and MLN); CD4+, CD8+ T cells and NK cells were found within secondary murine lymphoid organs. Post vaccination (12-13 week old) human engraftment of peripheral blood was observed ranging from 15%-79%. In an ELISPOT for IFN-γ, PECs from NSG-hu vaccinated with 293-gp96Ig-HIVgag i.p. generated an HIV specific immune response when stimulated with SLYNTVATL peptide, producing an average of 778 spots per 2x105 cells plated whereas mice vaccinated with 293 cells alone generated an average of 88.5 spots per 2x105 cells plated (p<0.05) We conclude that NSG-hu mice are able to establish and maintain stable hematopoiesis from human derived cells CD34+ cells. Furthermore, NSG-hu mice are capable of mounting a human HIV-specific immune response after gp96 vaccination.