Center for Human Immunology

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

In response to the SARS-CoV-2 pandemic we have made the technologies and platforms at CHI available for characterization of COVID-19 patient samples, as a priority ahead of our ongoing collaborative studies. CHI has contributed to 4 separate studies related to COVID-19 this fiscal year. To address adverse reactions to Covid mRNA vaccination CHI is currently running transcriptomics and serum proteomics for a cohort collected by Pamela Guererrio. In the context of therapeutic intervention in acute infection CHI identified 800 samples from the ACTT3 trial led by John Beigel for serum proteomic analysis, and is using this data to address how disease severity impacts outcomes. To analyse infection in children and lymph nodes, in collaboration with Kalpana Manthiparam, CHI has helped to generate CITE-seq and analyse cytometry from tonsil samples of infected subjects. To investigate longer term consequences of Covid infection, using a Tsang lab cohort, CHI performed high-dimensional cytometry characterizing responses with panels including staining for antigen-specific cells. In addition to this COVID work CHI has continued to advance its previous studies, which have a broader focus of multi-modal high-dimensional immune phenotyping of primary human samples, and include characterizing immune changes in vaccine trials (influenza, HSV, malaria), clinical intervention studies (diet, antibiotics, hypertension), and cohort studies of rare genetic diseases (mitochondrial or immune signaling dysfunction). The influenza vaccination study is an example of an integrated design involving a clinical trial and also parallel analysis for cross-validation at Stanford University. This began with broad phenotyping which was then further developed with CITE-seq to reveal acute and persistent impacts of vaccination, and has resulted in a manuscript reviewed at Cell. The HSV vaccine candidate study is an example where CHI was able to drive a systems level analysis using uniquely positioned samples from an NIH clinical trial, which enabled assessment of how effects of gender and prior exposure interact in vivo to shape an immune response, and has received a favourable review at ELife. Another study of note is a collaboration with Kevin Hall at NIDDK to characterize immune differences after periods of highly controlled diet changes, an example of exploratory unbiased analyses where peripheral blood transcriptomic, cytometry, and proteomic phenotypes have all shown differences as a result of the diet changes. To support CHIs mission we continue to develop wet-lab and computational infrastructure. For serum proteoics we have completed transition of our SomaLogic platform from a 1.3k antigen panel to an analysis of 7k antigens, and are testing novel sample types for this assay such as urine and saliva. For single cell sequencing technologies using the 10x platform, we have established a CITE-seq workflow which can now be run independently by CHI staff. For flow cytometry, on the Cytek Aurora we have continued to validate >30 color cytometry panels including for markers of cell types and responses of interest for our collaborators, such as neutrophils in the case of oral tissues. For mass cytometry analysis we are finalising a package that uses high dimensional observations to discriminate only the subset of cells that respond in ex vivo stimulation assays. This will become increasingly important as high-dimensional assays expand, such as our mass cytometry assay that quantifies phosphorylation of 10 intracellular proteins in addition to 20 cell phenotype markers, in response to 12 in vitro stimulation conditions.