Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 203, Issue 3, Pages 607-617Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20052005
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Funding
- NIAID NIH HHS [R01 AI013013, U19 AI062623, R01 AI041111, AI40874, R01 AI040874, R01 AI41111, AI13013] Funding Source: Medline
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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)-gamma- 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-gamma-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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