Icahn School of Medicine at Mount Sinai

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Grant title: Viral immunity and vaccination (VIVA) human immunology project consortium (HIPC)

Grant number: 1U19AI168631

Lead institution: Icahn School of Medicine at Mount Sinai

Center PI(s): Ana Fernandez-Sesma and Viviana Simon

The Viral Immunity and Vaccination (VIVA) Human Immunology Project Consortium (HIPC) will carry out a comprehensive systems immunology program to assess the dynamic human immune response to SARS-CoV-2, seasonal influenza viruses and tetravalent and trivalent dengue vaccines and subsequent infections by those pathogens. It will generate comprehensive innate, cellular and adaptive immune signatures that correlate with vaccine outcomes. The VIVA HIPC will leverage recent advances in human immune profiling methods to characterize the diverse states of the human immune system before and after vaccination against these viral pathogens of great public health concern using novel immune phenotyping and genomics strategies that generate data and tools to be used for downstream data analysis and functional investigations. The proposed studies will use longitudinal biospecimens from established human cohorts of respiratory infections and vaccinations in the US and Argentina as well as from vaccine trials in the US (provided by the Clinical Core, Core B). In addition, validation experiments using human tonsils sourced from healthy individuals and exposed ex vivo to the different vaccine types will be conducted. Three complementary, well-integrated projects will produce in-depth human immune profiles and signatures of SARS-CoV-2 vaccinations and infections (Project 1), seasonal influenza vaccinations and infections (Project 2) as well as dengue vaccine and human challenge studies (Project 3). Unique in our approach is the use of longitudinal cohorts for in vivo profiling, supported by ex vivo human tonsillar histoculture (HC) models for infection and vaccination. Our holistic approach will provide cutting-edge standardized and qualified ‘omics’ assays to assess cellular and serological immune responses to vaccinations and infections by the Immune Phenotyping Core (Core C), genomics/transcriptomics, including scRNAseq, CITEseq and spatial tissue transcriptomics by the Genomics Core (Core D), and experimental vaccinations in primary human tonsillar histocultures (HC) in Projects 1, 2 and 3. Data mining, bioinformatics analyses across data sets, and modeling for integration of the ‘omics’ datasets to identify the network components and infer their interactions and correlations important for vaccine outcomes will be done by the Data management and Analysis Core (Core E). The VIVA HIPC will make the data, analyses and immune profiles generated available to the scientific community by coupling our local data infrastructure to ImmPort (directly or through the HIPC Coordinating Center). This integration will ensure full and timely release of clinical, sample, and experimental metadata in synchrony with genomic data releases to standard data repositories including SRA, GEO, and Genbank (Core E). The VIVA team (Drs. Krammer, Garcia-Sastre, Durbin, Gamarnik, van Bakel and Sebra) led by Dr. Fernandez-Sesma and Dr. Simon includes physicians, physician scientists and scientists with complementary expertise in viral immunology, viral pathogenesis, vaccinology, genomics, data analysis and a proven track record of collaboration and excellence,