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

Chun I. Yu, Michael Gallegos, Florentina Marches, Gerard Zurawski, Octavio Ramilo, Adolfo García-Sastre, Jacques Banchereau, A. Karolina Palucka

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

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 nonobese diabetic severe combined immunodeficiency (NOD/SCID) β2 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 vaccine induces expansion of CD8 + T cells specific to influenza matrix protein (FluM1) and nonstructural protein 1 in blood, spleen, and lungs. On 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 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 that cannot be tested in human volunteers.

Original languageEnglish
Pages (from-to)3671-3678
Number of pages8
JournalBlood
Volume112
Issue number9
DOIs
StatePublished - 1 Nov 2008

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