This program project grant is a new proposal to develop vaccines by the Steinman-Nussenzweig-Ravetch laboratories. It is focused on investigating the hypothesis that antigens delivered directly to dendritic cells in conjunction with a maturation stimulus will enhance immunity and elicit productive immune responses to vaccine antigens. The program will exploit the principles of dendritic cell biology and immunology more broadly to design and develop vaccines, including phase I studies in humans.
Specific aims are: 1) Develop DNA vaccines that incorporate dendritic cell targeting strategies and test the vaccines in humans 2) Regulate FcR signaling on DC subsets as a means of controlling DC maturation and the generation of antigen-specific immnunity. 3) Identify antigens that induce broadly neutralizing anti-HIV-1 antibodies by cloning such antibodies from single B cells from rare individuals that control their HIV-I infection and controls that do not All of the projects proposed in this program will address these three areas using the complementary strategies outlined in the proposal. The information generated by each project will allow the group as a whole to adjust its strategy accordingly. Thus, the strength of the proposed program project lies in the expertise of the investigators, the proven record of their collaborations with other members of the program, and the close relationship each project has to the overall goals of the program.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI081677-05
Application #
8523749
Study Section
Special Emphasis Panel (ZAI1-KS-I (S3))
Program Officer
Quill, Helen R
Project Start
2009-09-25
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2013
Total Cost
$1,696,945
Indirect Cost
$664,912
Name
Rockefeller University
Department
Microbiology/Immun/Virology
Type
Other Domestic Higher Education
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
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Pantel, Austin; Teixeira, Angela; Haddad, Elias et al. (2014) Direct type I IFN but not MDA5/TLR3 activation of dendritic cells is required for maturation and metabolic shift to glycolysis after poly IC stimulation. PLoS Biol 12:e1001759
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Mollah, Shamim A; Dobrin, Joseph S; Feder, Rachel E et al. (2014) Flt3L dependence helps define an uncharacterized subset of murine cutaneous dendritic cells. J Invest Dermatol 134:1265-75
Gruell, Henning; Bournazos, Stylianos; Ravetch, Jeffrey V et al. (2013) Antibody and antiretroviral preexposure prophylaxis prevent cervicovaginal HIV-1 infection in a transgenic mouse model. J Virol 87:8535-44
Klein, Florian; Mouquet, Hugo; Dosenovic, Pia et al. (2013) Antibodies in HIV-1 vaccine development and therapy. Science 341:1199-204

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