vaccinated with influenza virus vaccines Broad influenza-specific CD8+ T-cell responses in humanized mice

ABSTRACT The development of novel human vaccines would be greatly facilitated by the development of in vivo models that permit preclinical analysis of human immune responses. Here, we show that non-obese diabetic severe combined immunodeficiency (NOD/SCID) β 2 microglobulin -/- mice, engrafted with human CD34 + hematopoietic progenitors and further reconstituted with T cells, can mount specific immune responses against influenza virus vaccines. Live attenuated trivalent influenza virus (LAIV) vaccine induces expansion of CD8 + T cells specific to influenza matrix protein (FluM1) and non-structural protein 1 (NS1) in blood, spleen and lungs. Upon ex vivo exposure to influenza antigens, antigen-specific CD8 + T cells produce IFN-γ and express cell-surface CD107a. FluM1-specific CD8 + T cells can be also expanded in mice vaccinated with inactivated trivalent influenza virus (TIV) vaccine. Expansion of antigen-specific CD8 + T cells is dependent on reconstitution of the human myeloid compartment. Thus, this humanized mouse model permits preclinical testing of vaccines designed to induce cellular immunity including those against influenza virus. Furthermore, this work sets the stage for systematic analysis of the in vivo functions of human DCs. This, in turn will allow a new approach to the rational design and preclinical testing of vaccines which cannot be tested in human volunteers. From bloodjournal.hematologylibrary.org by guest on June 3, 2013. For personal use only.