La Jolla Institute for Allergy and Immunology

Project #:1-U19-AI-118626-01

Title: Human immune signatures of Dengue virus and Mycobacterium Tuberculosis exposure in infection, disease and vaccination

PI: Alessandro D. Sette

MSSM

Primary Projects IOF Projects

The HIPC center at the La Jolla Institute is elucidating T cell signatures of protection from and susceptibility to disease in an unbiased manner. To gain a broad understanding of T cell responses, both a bacterial (tuberculosis) and a viral (dengue) disease will be studied, using samples from geographically and ethnically diverse cohorts. These pathogens were also chosen for their global health significance; this work has high potential to inform the development and testing of improved vaccines, as T cells are known to be key for protective immunity against both tuberculosis and dengue. The two projects have parallel designs, defining and comparing various T cell subsets from cohorts with past or latent infection, active disease, and vaccination (with an experimental dengue vaccine or the yellow fever vaccine for the dengue studies and with the BCG vaccine for tuberculosis).

The fundamental impact of this research will be greater insight into whether infection and vaccination lead to expansion or contraction of subsets already present within the individual’s T cell pool that maintain their phenotype, and/or lead to differentiation or activation of T cells into states uniquely associated with those conditions.

Primary Projects

Human immune signatures of natural immunity to DENV infection, severe disease, and vaccination with attenuated live vaccine

Project Leader: Alessandro D. Sette

Institution: La Jolla Institute for Allergy and Immunology

Human immune signatures of latent MTB infection, active disease and BCG vaccination

Project Leader: Bjoern Peters

Institution: La Jolla Institute for Allergy and Immunology

Epigenomics of DENV and MTB

Project Leader: Pandurangan Vijayanand

Institution: La Jolla Institute for Allergy and Immunology

Sequencing Core

Project Leader: Gregory Seumois

Institution: La Jolla Institute for Allergy and Immunology

Clinical Core

Project Leader: Pandurangan Vijayanand

Institution: La Jolla Institute for Allergy and Immunology

Data Management Core

Project Leader: Bjoern Peters

Institution: La Jolla Institute for Allergy and Immunology

IOF Projects

Shared resource for micro-scaled epigenetic assays

Project Leader: Pandurangan Vijayanand

Institution: La Jolla Institute for Allergy and Immunology

Shared resource for functional genomics

Project Leader: Sonia Sharma

Institution: La Jolla Institute for Allergy and Immunology

Phenotyping and mRNA profiling of pertussis-specific CD4 T cells induced by acellular versus whole-cell vaccines associated with differential protective efficacy

Project Leader: Alessandro D. Sette

Institution: La Jolla Institute for Allergy and Immunology

Single-cell RNA-Seq analysis of MTB and DENV immune responses

Project Leader: Pandurangan Vijayanand

Institution: La Jolla Institute for Allergy and Immunology