# Assessing the determinants of durable protective immunity in SARS-CoV-2 infected human subjects

> **NIH NIH U01** · SEATTLE CHILDREN'S HOSPITAL · 2020 · $338,565

## Abstract

PROJECT SUMMARY
Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus has already resulted in nearly 3
million laboratory diagnosed infections and over 200,000 deaths worldwide. There is no known pre-existing
immunity to SARS-CoV-2 in humans or licensed therapeutics to combat or limit infection. In the absence of
these pharmacological interventions, governments around the world have implemented stringent measures to
that curb the spread of SARS-CoV-2 to populations at risk of serious complications from infection. Efforts to
identify efficacious therapies and develop vaccines to counter infection and disease require time and ultimately
need to be guided by deep knowledge about this novel pathogen. Immune-directed therapies in particular
require a detailed understanding of the immune responses generated not only in severe COVID-19 disease but
also in the vast majority of individuals who develop non-severe disease. Innate immunity serves as the frontline
response to counter the early stages of infection and but is also critical for regulating the ensuing adaptive
immune response. In humans, anti-SARS-CoV-2 humoral immunity has gained significant attention while roles
for innate immunity and memory T cell responses have not been extensively studied. However, knowledge
gained from SARS-CoV-1 studies indicate that T cell immunity is critical in virus control. In these SARS-CoV-1
infected mice, the induction of the innate type I Interferon signaling cascade is delayed. Yet mice lacking this
innate immune response exhibited greater numbers of virus specific T cells in their lungs. Thus, this
dysregulated innate immune response impairs anti-SARS-CoV-1 T cell memory. Whether SARS-CoV-2
infection induces protective memory T cells and if the durability of anti-SARS-CoV-2 T cell memory is
influenced by innate immunity are all currently unexplored. In humans, the innate immune response induced in
non-severe COVID-19 disease is not well characterized. However, preliminary studies in cultured cells and
animal models indicate that upon SARS-CoV-2 infection, there is a restricted and delayed induction of innate
immunity resulting in limited induction of cytokines and chemokines critical for immune cell recruitment. We
predict that the vast majority of COVID-19 infected individuals will exhibit a dysregulated innate immune
response typified by delayed and limited inflammatory signaling. If true, such a compromised innate immune
response could in turn induce limited short-lived adaptive immunity. Indeed, studies from SARS-CoV-1
infections indicate that humoral responses are short-lived in recovered patients. To our knowledge, no studies
have examined memory durability in COVID-19 subjects. In this proposal, we will interrogate samples from a
prospective longitudinal cohort of Seattle residents to examine if aberrant T cell memory is induced during
SARS-CoV-2 infection and importantly if this impaired memory stems from dysregulated innate immunity.
Furth...

## Key facts

- **NIH application ID:** 10146155
- **Project number:** 3U01AI142001-02S1
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Stefan HI Kappe
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $338,565
- **Award type:** 3
- **Project period:** 2020-07-06 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146155

## Citation

> US National Institutes of Health, RePORTER application 10146155, Assessing the determinants of durable protective immunity in SARS-CoV-2 infected human subjects (3U01AI142001-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10146155. Licensed CC0.

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