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)-γ– 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-γ–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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20 March 2006
Article|
February 27 2006
Intensified and protective CD4+ T cell immunity in mice with anti–dendritic cell HIV gag fusion antibody vaccine
Christine Trumpfheller,
Christine Trumpfheller
1Laboratory of Cellular Physiology and Immunology
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Jennifer S. Finke,
Jennifer S. Finke
1Laboratory of Cellular Physiology and Immunology
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Carolina B. López,
Carolina B. López
3Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029
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Thomas M. Moran,
Thomas M. Moran
3Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029
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Bruno Moltedo,
Bruno Moltedo
3Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029
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Helena Soares,
Helena Soares
1Laboratory of Cellular Physiology and Immunology
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Yaoxing Huang,
Yaoxing Huang
4The Aaron Diamond AIDS Research Center, New York, NY 10016
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Sarah J. Schlesinger,
Sarah J. Schlesinger
1Laboratory of Cellular Physiology and Immunology
4The Aaron Diamond AIDS Research Center, New York, NY 10016
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Chae Gyu Park,
Chae Gyu Park
1Laboratory of Cellular Physiology and Immunology
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Michel C. Nussenzweig,
Michel C. Nussenzweig
2Laboratory of Molecular Immunology, Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10021
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Angela Granelli-Piperno,
Angela Granelli-Piperno
1Laboratory of Cellular Physiology and Immunology
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Ralph M. Steinman
Ralph M. Steinman
1Laboratory of Cellular Physiology and Immunology
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Christine Trumpfheller
1Laboratory of Cellular Physiology and Immunology
Jennifer S. Finke
1Laboratory of Cellular Physiology and Immunology
Carolina B. López
3Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029
Thomas M. Moran
3Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029
Bruno Moltedo
3Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029
Helena Soares
1Laboratory of Cellular Physiology and Immunology
Yaoxing Huang
4The Aaron Diamond AIDS Research Center, New York, NY 10016
Sarah J. Schlesinger
1Laboratory of Cellular Physiology and Immunology
4The Aaron Diamond AIDS Research Center, New York, NY 10016
Chae Gyu Park
1Laboratory of Cellular Physiology and Immunology
Michel C. Nussenzweig
2Laboratory of Molecular Immunology, Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10021
Angela Granelli-Piperno
1Laboratory of Cellular Physiology and Immunology
Ralph M. Steinman
1Laboratory of Cellular Physiology and Immunology
CORRESPONDENCE Ralph M. Steinman: [email protected]
Received:
October 06 2005
Accepted:
February 01 2006
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2006
J Exp Med (2006) 203 (3): 607–617.
Article history
Received:
October 06 2005
Accepted:
February 01 2006
Connected Content
Citation
Christine Trumpfheller, Jennifer S. Finke, Carolina B. López, Thomas M. Moran, Bruno Moltedo, Helena Soares, Yaoxing Huang, Sarah J. Schlesinger, Chae Gyu Park, Michel C. Nussenzweig, Angela Granelli-Piperno, Ralph M. Steinman; Intensified and protective CD4+ T cell immunity in mice with anti–dendritic cell HIV gag fusion antibody vaccine . J Exp Med 20 March 2006; 203 (3): 607–617. doi: https://doi.org/10.1084/jem.20052005
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