Cross‐presentation of Influenza virus vaccine antigens to CD8+ T cells in humanized mice

Abstract

Critical to the development of novel vaccines is the availability of in vivo models of the human immune system that permit testing of vaccine efficacy. Here, we used NOD/SCID beta2m −/− immunodeficient mice which, when engrafted with human CD34+ hematopoietic progenitors, develop all subset of human dendritic cells (DCs) and B cells. T cells and their subsets can be reconstituted by adoptive transfer. We show that these mice can generate recall CD8+ T cell responses upon exposure to seasonal influenza virus vaccines i) live attenuated trivalent vaccine, i.e. FluMist; or ii) killed trivalent vaccine, i.e., Fluzone. CD8+ T cells specific to at least two influenza antigens FluM1 and NS1 can be detected in the blood of mice vaccinated with FluMist but not in mice vaccinated with Fluzone. Specific T cells are also present in the spleen and peripheral tissues (lung) demonstrating that human T cells can utilize murine signals for trafficking and extravasation. Upon short‐term ex vivo antigen exposure CD8+ T cells produce IFN‐g and express surface CD107 consistent with their acquisition of effector function. Response to vaccination is dependent upon reconstitution of the human hematopoietic system. Thus, vaccine antigens can be cross‐presented by endogenous human antigen presenting cells in humanized mice. Therefore, this model might be useful for testing vaccines oriented towards generation of cellular immunity.