Antiviral lung resident memory T cell maintenance and reinvigoration

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

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Principal Investigator: Mariah A Hassert
Organization: UNIVERSITY OF IOWA
Fiscal Year: 2024
Award: $74,284
Funding agency: National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY
Seasonal influenza A (IAV) and other airborne viral pathogens such as SARS-CoV-2 represent a substantial
burden on global public health. While sterilizing immunity can be attained through neutralizing antibodies,
seasonal antigenic drift permits viral evasion of humoral immunity, which necessitates annual reformulation of
the seasonal influenza vaccine. It has previously been shown, that cross-reactive CD8+ T cells can provide
heterosubtypic non-sterilizing immunity to IAV. However, this cross-protection is relatively short-lived in the
context of a singular antigen exposure. Our lab has shown that lung tissue resident memory T cells (lung Trm)
contribute to this strain transcending cross-protection and that the waning in numbers of IAV-specific Trm strongly
correlate with this loss of IAV cross-protection. Importantly, we have found that multiple exposures to the same
IAV antigens (boosting) can extend the longevity of these lung Trm populations, and as a result, provide extended
heterosubtypic immunity. There still exists a substantial knowledge gap regarding why lung Trm cells are so short
lived when they are clearly important for protection. Addressing this question remains a critical step in the rational
design of universal influenza vaccines. Our long-term goal is to understand the biology that underlies the
waning of lung Trm cells and to harness this information to aid in the development of broadly protective
influenza vaccines. We will address this long-term goal with the following specific aims:
Aim 1: Determine the molecular T cell intrinsic factors that permit extended longevity and functionality of lung
Trm following multiple antigen exposures.
Aim 2: Define the optimal priming and boosting vaccination strategies to maximize Trm generation, re-
invigoration, and function.

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