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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Type
Research Program Projects (P01)
Project #
5P01AI104715-02
Application #
8616339
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Moyer, Tyson J; Zmolek, Andrew C; Irvine, Darrell J (2016) Beyond antigens and adjuvants: formulating future vaccines. J Clin Invest 126:799-808
Deruaz, Maud; Moldt, Brian; Le, Khoa M et al. (2016) Protection of Humanized Mice From Repeated Intravaginal HIV Challenge by Passive Immunization: A Model for Studying the Efficacy of Neutralizing Antibodies In Vivo. J Infect Dis 214:612-6
Ranasinghe, Srinika; Lamothe, Pedro A; Soghoian, Damien Z et al. (2016) Antiviral CD8(+) T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion. Immunity 45:917-930
Garcia-Beltran, Wilfredo F; Hölzemer, Angelique; Martrus, Gloria et al. (2016) Open conformers of HLA-F are high-affinity ligands of the activating NK-cell receptor KIR3DS1. Nat Immunol 17:1067-74
Liu, Haipeng; Irvine, Darrell J (2015) Guiding principles in the design of molecular bioconjugates for vaccine applications. Bioconjug Chem 26:791-801
Karpel, Marshall E; Boutwell, Christian L; Allen, Todd M (2015) BLT humanized mice as a small animal model of HIV infection. Curr Opin Virol 13:75-80
Altfeld, Marcus; Gale Jr, Michael (2015) Innate immunity against HIV-1 infection. Nat Immunol 16:554-62
Hotaling, Nathan A; Tang, Li; Irvine, Darrell J et al. (2015) Biomaterial Strategies for Immunomodulation. Annu Rev Biomed Eng 17:317-49
Liu, Haipeng; Moynihan, Kelly D; Zheng, Yiran et al. (2014) Structure-based programming of lymph-node targeting in molecular vaccines. Nature 507:519-22
Pejawar-Gaddy, Sharmila; Kovacs, James M; Barouch, Dan H et al. (2014) Design of lipid nanocapsule delivery vehicles for multivalent display of recombinant Env trimers in HIV vaccination. Bioconjug Chem 25:1470-8

Showing the most recent 10 out of 17 publications