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¹ Laboratory of Cellular Physiology and Immunology and ² Laboratory of Molecular Immunology, Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10021
³ Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029
⁴ The Aaron Diamond AIDS Research Center, New York, NY 10016

CORRESPONDENCE Ralph M. Steinman: steinma{at}mail.rockefeller.edu

Current human immunodeficiency virus (HIV) vaccine approaches emphasize prime boost strategies comprising multiple doses of DNA vaccine and recombinant viral vectors. We are developing a protein-based approach that directly harnesses principles for generating T cell immunity. Vaccine is delivered to maturing dendritic cells in lymphoid tissue by engineering protein antigen into an antibody to DEC-205, a receptor for antigen presentation. Here we characterize the CD4⁺ T cell immune response to HIV gag and compare efficacy with other vaccine strategies in a single dose. DEC-205–targeted HIV gag p24 or p41 induces stronger CD4⁺ T cell immunity relative to high doses of gag protein, HIV gag plasmid DNA, or recombinant adenovirus-gag. High frequencies of interferon (IFN)-– and interleukin 2–producing CD4⁺ T cells are elicited, including double cytokine-producing cells. In addition, the response is broad because the primed mice respond to an array of peptides in different major histocompatibility complex haplotypes. Long-lived T cell memory is observed. After subcutaneous vaccination, CD4⁺ and IFN-–dependent protection develops to a challenge with recombinant vaccinia-gag virus at a mucosal surface, the airway. We suggest that a DEC-targeted vaccine, in part because of an unusually strong and protective CD4⁺ T cell response, will improve vaccine efficacy as a stand-alone approach or with other modalities.

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