The goal of this core is to serve Projects 1 and 2, by identifying HLA class I and class II epitopes derived from VZV, as a necessary prelude to the analyses of the dynamics of the epitope-specific T cell responses to vaccination with the zoster vaccine (Project 2). This data generated on the epitope specific T cell responses will be critical in evaluating the innate signatures that correlate with, and predict, the magnitude of the epitope specific T cell responses in Project 1. A key question that will be facilitated by the information generated in this core, is whether early innate signatures are capable of predicting the """"""""breadth"""""""" of the T cell responses to zoster vaccinafion in the elderly. Accordingly, our specific aims are:
Aim 1. Prediction and synthesis of candidate VZV HLA class I and class II epitopes We will screen the VZV proteome for the presence of sequence motifs associated with binding to 12 different HLA class I and 9 different HLA class II molecules, representafive of main HLA supertypes, and representative of the majority of HLA class I and class II molecules expressed in different ethnicities woridwide. Prediction of epitopes restricted by of a broad range of prevalent HLA molecules and supertypes will ensure adequate populafion coverage, thus enabling a rigorous evaluation of T cell responses associated with infecfion and vaccinafion in humans.
Aim 2. Test validated epitopes for binding to purified HLA molecules In vitro Project 2 will be mainly responsible for epitope validation and characterizafion, and as such those acfivities are neither described in detail nor budgeted for in the present secfion describing this core. In this core, we will test the validated/identified epitopes for binding to HLA molecules in vitro, thus enabling projection of their use in different ethnicities.
Aim 3. Data handling and Epitope submission In terms of submission of epitope data to the lEDB, we already have in-house the capability to prepare and submit data in the required XML format, as the proposed PI of this core is also the PI of the lEDB project. We anticipate being able to easily submit the identified epitopes to the lEDB, as we have already accomplished this task in the context of several previous epitope identiflcation projects.

Public Health Relevance

The goal of this core is to identify the epitopes recognized by antigen-specific T cells that respond to zoster vaccine or infection. This will be a prelude to the analysis of epitope specific T cell responses to vaccination, and facilitate the identification of innate signatures that predict the breadth of the T cell response.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI090023-05
Application #
8688045
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Emory University
Department
Type
DUNS #
City
Atlanta
State
GA
Country
United States
Zip Code
Upadhyay, Amit A; Kauffman, Robert C; Wolabaugh, Amber N et al. (2018) BALDR: a computational pipeline for paired heavy and light chain immunoglobulin reconstruction in single-cell RNA-seq data. Genome Med 10:20
Bowen, James R; Zimmerman, Matthew G; Suthar, Mehul S (2018) Taking the defensive: Immune control of Zika virus infection. Virus Res 254:21-26
Woodruff, Matthew Charles; Kim, Eui Ho; Luo, Wei et al. (2018) B Cell Competition for Restricted T Cell Help Suppresses Rare-Epitope Responses. Cell Rep 25:321-327.e3
Yu, Tianwei (2018) A new dynamic correlation algorithm reveals novel functional aspects in single cell and bulk RNA-seq data. PLoS Comput Biol 14:e1006391
Sullivan, Nicole L; Reuter-Monslow, Morgan A; Sei, Janet et al. (2018) Breadth and Functionality of Varicella-Zoster Virus Glycoprotein-Specific Antibodies Identified after Zostavax Vaccination in Humans. J Virol 92:
Lynn, David J; Pulendran, Bali (2018) The potential of the microbiota to influence vaccine responses. J Leukoc Biol 103:225-231
Yu, Tianwei (2018) Nonlinear variable selection with continuous outcome: a fully nonparametric incremental forward stagewise approach. Stat Anal Data Min 11:188-197
Levin, Myron J; Cai, Guang-Yun; Lee, Katherine S et al. (2018) Varicella-Zoster Virus DNA in Blood After Administration of Herpes Zoster Vaccine. J Infect Dis 217:1055-1059
Hagan, Thomas; Pulendran, Bali (2018) Will Systems Biology Deliver Its Promise and Contribute to the Development of New or Improved Vaccines? From Data to Understanding through Systems Biology. Cold Spring Harb Perspect Biol 10:
Kang, Hyun Min; Subramaniam, Meena; Targ, Sasha et al. (2018) Multiplexed droplet single-cell RNA-sequencing using natural genetic variation. Nat Biotechnol 36:89-94

Showing the most recent 10 out of 105 publications