This Program Project Grant (PPG) builds on the investigators strong track records in understanding neutralizing antibody and CD8+ T cell responses against HIV, the development of novel nanoparticle delivery appraoches and translates these efforts into a newly developed BLT (bone marrow, liver, thymus) humanized mouse model of HIV infection. Critical to the success of this POl is an Administrative and Biostatistics Core facility provide not only scientific and administrative leadership in coordinating the two Projects and three Cores that make up this effort, but also to coordinate the acquisition, storage, and retrieval of samples from vaccinated and challenged humanized mice for each of the individual projects that fuel the research, to insure quality processing and storage of these valuable samples, to maintain a database to support the goals of this program, and to provide biostatistical support that will allow integration of clinical, immunologic and virologic data for the highly complementary projects that make up this POl. These efforts will occur in parallel, but in a coordinated and highly integrated fashion that allows for information from each of the efforts to continually guide and inform the others. Specifically, we propose that the Administrative and Biostatistics Core will: 1. Provide scientific leadership and project management for all aspects of the grant. 2. Provide administrative and financial oversight. 3. Provide biostatistical support for all aspects of the program. 4. Recruit a Scientific Advisory Board and host an annual meeting. 5. Maintain a database of clinical, immunological, and virological data from BLT mice.
The newly developed humanized mouse model provides the unique opportunity to explore the correlates of immune protection of HIV by cellular and humoral immune responses within a system capable of supporting HIV infection and mounting human HIV-specific type responses. This model will also enable us to rapidly test iterative vaccine design approaches to optimize cellular and humoral immune responses to HIV.
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|Liu, Haipeng; Moynihan, Kelly D; Zheng, Yiran et al. (2014) Structure-based programming of lymph-node targeting in molecular vaccines. Nature 507:519-22|
|Körner, Christian; Granoff, Mitchell E; Amero, Molly A et al. (2014) Increased frequency and function of KIR2DL1-3? NK cells in primary HIV-1 infection are determined by HLA-C group haplotypes. Eur J Immunol 44:2938-48|
|Seung, Edward; Dudek, Timothy E; Allen, Todd M et al. (2013) PD-1 blockade in chronically HIV-1-infected humanized mice suppresses viral loads. PLoS One 8:e77780|
|Tager, Andrew M; Pensiero, Michael; Allen, Todd M (2013) Recent advances in humanized mice: accelerating the development of an HIV vaccine. J Infect Dis 208 Suppl 2:S121-4|
|Seung, Edward; Tager, Andrew M (2013) Humoral immunity in humanized mice: a work in progress. J Infect Dis 208 Suppl 2:S155-9|
|Lavender, Kerry J; Pang, Wendy W; Messer, Ronald J et al. (2013) BLT-humanized C57BL/6 Rag2-/-?c-/-CD47-/- mice are resistant to GVHD and develop B- and T-cell immunity to HIV infection. Blood 122:4013-20|
|Dudek, Timothy E; Allen, Todd M (2013) HIV-specific CD8ýýý T-cell immunity in humanized bone marrow-liver-thymus mice. J Infect Dis 208 Suppl 2:S150-4|