The overall goal of the Program Project structure is to provide an environment that fosters detailed, multi- disciplinary characterization of the development of virus-specific and cross-reactive (XR) CDS+ T cells, using the Epstein Barr virus (EBV) model of human infection. Each project in this Program Project is interdependent with regard to expertise, resources, and experimental design and requires access to high- quality clinical specimens and similar technologies. Core A will provide the necessary scientific leadership (including Internal and External Advisory Boards) and administrative and fiscal support to facilitate these multi-disciplinary, collaborative studies. These multidisciplinary studies will result in large and diverse data sets;experts in bioinformatics and biostatistics will not only assist in the development of an integrated database but will also help develop and apply appropriate analytical approaches. In the absence of a suitable animal model, human studies are essential. The University of Massachusetts Amherst (UMA) Health Services Acute Infectious Mononucleosis (AIM) Clinic provides essential clinical samples and constitutes one of a very few longitudinal AIM cohorts in the world. Over the years, we have altered clinical visit and sample collection schedules to address evolving scientific questions. While the AIM Clinic remains the main source of our clinical samples, the newly created UMA EBV Serosurveillance Cohort will allow us to obtain updated estimates of EBV seropositivity and seroconversion in college students. Work conducted over the past funding period has identified high frequencies of influenza and EBV XR CD8+ T cells in the circulation of a small group of individuals who remain EBV uninfected into their third decade of life and beyond. This has led to a novel hypothesis (i.e., that high frequencies of these cross-reactive CDS+ T cells might protect against EBV infection) and organization of a new cohort (EBV Seronegative;EBV-SN) that will be recruited to address this new hypothesis in the next funding period.

Public Health Relevance

The proposed studies will investigate factors that control the evolution of human antiviral CD8+ T cell responses from the acute effector phase into long-term memory and how antigen-specific or cross-reactive CD8+ T cells contribute to viral control or disease. We hope that they will inform the development of antiviral vaccines that afford long-term protection against infection or disease, while minimizing potential adverse effects. By providing scientific leadership, administrative and fiscal support, an integrated database/data analysis, and unique clinical samples. Core A is essential to the Program Project's overall success.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI049320-12
Application #
8567607
Study Section
Special Emphasis Panel (ZAI1-PA-I)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
12
Fiscal Year
2013
Total Cost
$380,317
Indirect Cost
$113,289
Name
University of Massachusetts Medical School Worcester
Department
Type
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655
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