The influenza virus and its variants remains a serious public health threat in both developing and developed counties, accounting for ~35,000 deaths and hundreds of thousands hospitalized in the US alone in an average year. In this renewal application from the Cooperative Center for Human Immunology at Stanford University, we wish to leverage our considerable experience in analyzing the influenza vaccine response to address some fundamental questions and hypotheses regarding how the human immune system responds to influenza vaccination or infection. We also wish to continue advancing immune monitoring technologies relevant to analyzing the human immune response, such Cytometry by Time-Of-Flight, or CyTOF, combinatorial peptide-MHC tetramers and new TCR and BCR repertoire and gene expression analysis methods that open up entirely new areas of investigation and ways to test hypotheses. The general theme of our proposal is to address specific questions regarding how the human immune system develops and changes in young children, adolescents and young adults. While there are considerable challenges in monitoring the immune responses of infants and young children, new technologies, many of them developed here at Stanford, now make some very fundamental questions feasible to address. These include testing hypotheses about memory phenotype T cells, and of flu-specific effector and memory CD4+ T cells (PI), the influence of innate immune factors and CD4+ T cells on influenza virus infection in a novel ex vivo system (P2), the development of the immunoglobulin, T cell receptor and NK repertoires in response to vaccination in different age groups from our twin cohort (P3), and advancing the capabilities of the CyTOF instrument (P4). These efforts will be very ably supported by our Administrative (A), Pilot (B), Clinical (C), Human Immune Monitoring (D), Genomics (E) and Bioinformatics (F) Cores. Most of these cores have been in place for four or more years and have provided vital and state-of the-art support for the research activities of the group. We are entering into an exciting period of time for human immunology and we think that the Stanford team will continue to be extremely productive.

Public Health Relevance

Influenza virus is a category C priority human pathogen that represents an ongoing and serious public health threat world-wide. In this proposal we seek to understand the fundamental processes with which the human immune system responds to vaccination and combats influenza infection. We are particularly focused on how this immunity develops in children and adolescents compared to adults.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1)
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Ramachandra, Lakshmi
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Stanford University
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Furman, David; Chang, Junlei; Lartigue, Lydia et al. (2017) Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states. Nat Med 23:174-184
Vendrame, Elena; Fukuyama, Julia; Strauss-Albee, Dara M et al. (2017) Mass Cytometry Analytical Approaches Reveal Cytokine-Induced Changes in Natural Killer Cells. Cytometry B Clin Cytom 92:57-67
Jensen, Helle; Chen, Shih-Yu; Folkersen, Lasse et al. (2017) EBI3 regulates the NK cell response to mouse cytomegalovirus infection. Proc Natl Acad Sci U S A 114:1625-1630
Alcántara-Hernández, Marcela; Leylek, Rebecca; Wagar, Lisa E et al. (2017) High-Dimensional Phenotypic Mapping of Human Dendritic Cells Reveals Interindividual Variation and Tissue Specialization. Immunity 47:1037-1050.e6
de Bourcy, Charles F A; Angel, Cesar J Lopez; Vollmers, Christopher et al. (2017) Phylogenetic analysis of the human antibody repertoire reveals quantitative signatures of immune senescence and aging. Proc Natl Acad Sci U S A 114:1105-1110
Sweeney, Timothy E; Haynes, Winston A; Vallania, Francesco et al. (2017) Methods to increase reproducibility in differential gene expression via meta-analysis. Nucleic Acids Res 45:e1
Pardi, Norbert; Hogan, Michael J; Pelc, Rebecca S et al. (2017) Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination. Nature 543:248-251
Mukherjee, Sayak; Jensen, Helle; Stewart, William et al. (2017) In silico modeling identifies CD45 as a regulator of IL-2 synergy in the NKG2D-mediated activation of immature human NK cells. Sci Signal 10:
Glanville, Jacob; Huang, Huang; Nau, Allison et al. (2017) Identifying specificity groups in the T cell receptor repertoire. Nature 547:94-98
Raymond, Steven L; López, María Cecilia; Baker, Henry V et al. (2017) Unique transcriptomic response to sepsis is observed among patients of different age groups. PLoS One 12:e0184159

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