This program project grant (PPG) builds on an innovative strategy for AIDS vaccine development that takes advantage of the ability of recombinant rhesus CMV (RhCMV) vectors expressing SIV antigens to elicit long- lived, tissue-based effector memory T cell responses that are associated with localized and very early control of virus replication. The PPG brings together experienced investigators that provide complementary expertise in their projects with the common goals of designing, constructing and testing next generation RhCMV/SIV vaccine vectors with enhanced efficacy and safety. Core D will play a key role in supporting these efforts and integrating the different projects by the provision of standardized virology and immunology services and assays. Specifically, Core D will support the project-specific in vivo studies through production and characterization of recombinant RhCMV/SIV vectors, virus load monitoring, and evaluation of SIV antigen-specific T cell responses.

Public Health Relevance

The HIV/AIDS epidemic constitutes one ofthe most pressing public health threats in the world today, and an effective vaccine is urgently needed. The work proposed in this HIVRAD program will further explore and develop a highly innovative approach to HIV/AIDS vaccine development, exploiting the striking immunogenicity, persistence and genetic malleability of cytomegalovirus (CMV) to design a vaccine vector that elicits long-lived, tissue-based T cell responses that can provide early stringent control of AIDS-causing viruses. The Core lab proposed here (Core D) will provide routine virology and immunology services to this Program, including production of the CMV vaccines and provision of standardized assays for monitoring virus replication and secretion and SIV-specific T cell responses in the rhesus monkey model ofAIDS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI094417-03
Application #
8495915
Study Section
Special Emphasis Panel (ZAI1-BP-A)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
3
Fiscal Year
2013
Total Cost
$425,154
Indirect Cost
$147,375
Name
Oregon Health and Science University
Department
Type
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Child, Stephanie J; Hickson, Sarah E; Bayer, Avraham et al. (2018) Antagonism of the Protein Kinase R Pathway in Human Cells by Rhesus Cytomegalovirus. J Virol 92:
McMichael, Andrew J; Picker, Louis J (2018) Corrigendum to 'Unusual antigen presentation offers new insight into HIV vaccine design' [Curr Opin Immunol 46 (2017) 75-81]. Curr Opin Immunol 53:217
Wu, Helen L; Wiseman, Roger W; Hughes, Colette M et al. (2018) The Role of MHC-E in T Cell Immunity Is Conserved among Humans, Rhesus Macaques, and Cynomolgus Macaques. J Immunol 200:49-60
Walters, Lucy C; Harlos, Karl; Brackenridge, Simon et al. (2018) Pathogen-derived HLA-E bound epitopes reveal broad primary anchor pocket tolerability and conformationally malleable peptide binding. Nat Commun 9:3137
Früh, Klaus; Picker, Louis (2017) CD8+ T cell programming by cytomegalovirus vectors: applications in prophylactic and therapeutic vaccination. Curr Opin Immunol 47:52-56
McMichael, Andrew J; Picker, Louis J (2017) Unusual antigen presentation offers new insight into HIV vaccine design. Curr Opin Immunol 46:75-81
Hansen, Scott G; Wu, Helen L; Burwitz, Benjamin J et al. (2016) Broadly targeted CD8? T cell responses restricted by major histocompatibility complex E. Science 351:714-20
Hansen, Scott G; Sacha, Jonah B; Hughes, Colette M et al. (2013) Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms. Science 340:1237874
Hansen, Scott G; Piatak Jr, Michael; Ventura, Abigail B et al. (2013) Immune clearance of highly pathogenic SIV infection. Nature 502:100-4
Masopust, David; Picker, Louis J (2012) Hidden memories: frontline memory T cells and early pathogen interception. J Immunol 188:5811-7

Showing the most recent 10 out of 11 publications