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Principal Investigator: Ana Fernandez-Sesma
Organization: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
Fiscal Year: 2024
Award: $2,265,730
Funding agency: National Institute of Allergy and Infectious Diseases
SUMMARY
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- 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
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.
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2><SARSCoV2><Sampling><Scientist><Seasons><Serology><Serotyping><Severe Acute Respiratory Coronavirus><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV 2 vaccine><Severe Acute Respiratory Syndrome Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 vaccination><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 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vaccine><scRNA-seq><seasonal flu><seasonal influenza><secondary immune response><sequencing platform><severe acute respiratory syndrome-CoV><single cell RNA-seq><single cell RNAseq><single cell expression profiling><single cell transcriptomic profiling><single-cell RNA sequencing><tonsillar><tool><transcriptomics><vaccinate against COVID-19><vaccinate against SARS-CoV-2><vaccinate against coronavirus disease 2019><vaccinate against severe acute respiratory syndrome coronavirus 2><vaccinated individual><vaccinated participant><vaccinated patient><vaccinated person><vaccinated subject><vaccination against COVID-19><vaccination against SARS-CoV-2><vaccination against Severe acute respiratory syndrome coronavirus 2><vaccination against coronavirus disease 2019><vaccination against influenza><vaccination outcome><vaccination result><vaccination study><vaccination trial><vaccine against 2019-nCov><vaccine against COVID-19><vaccine against DENV><vaccine against SARS-CoV-2><vaccine against 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