Immune signatures of vaccine responses in vulnerable populations

NIH Pandemic-Era Grants

Pandemic Era Grants

2022

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Principal Investigator: David A. Hafler
Organization: YALE UNIVERSITY
Fiscal Year: 2022
Award: $2,874,261
Funding agency: National Institute of Allergy and Infectious Diseases

ABSTRACT
 We propose a deep interrogation and a systems approach that will identify molecular signatures to
vaccination across three cohorts of vulnerable patient populations: autoimmune patients with B cell depletion,
aged and frail individuals, and patients with sickle cell disease who are functionally asplenic. These distinct
populations share a dysregulated inflammatory milieu that is linked to poor vaccination responsiveness. We have
assembled an interdisciplinary team of investigators with a track record of longstanding and productive
collaborations to use a systems approach that combines well-defined and understudied cohorts with unbiased
large-scale profiling to elucidate signatures defining vaccine responsiveness. This goal will be accomplished by:
1) examining three vulnerable patient cohorts challenged with different vaccines, including novel mRNA vaccines
and one shared vaccine; 2) using shared platforms that deeply interrogate immune responses from blood and
limited-access compartments; and 3) refining new mathematical tools for multidimensional analysis of data to
identify active pathways and modules and to determine specific connections among components in the immune
network that contribute to differential vaccine effectiveness. This effort capitalizes on recent advances in single-
cell and spatial immune profiling methods along with shared immunologic and proteomic platforms to create a
novel public resource for vulnerable populations that characterizes diverse states of the human immune system.
Integration across our cohorts will support the development of molecular signatures of vaccination responses
and identify critical pathways relevant for potential therapeutic strategies.

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