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Principal Investigator: OFER LEVY
Organization: BOSTON CHILDREN'S HOSPITAL
Fiscal Year: 2020
Award: $308,143
Funding agency: National Institute of Allergy and Infectious Diseases
LAS PROJECT SUMMARY:
From a cluster of respiratory illnesses in Wuhan, China, to a worldwide pandemic, the world has learned of a
novel coronavirus (SARS-CoV-2) but little is known about the pathogenesis that leads to the disease termed
“COVID”. Patients with SARS-CoV-2 infection range from asymptomatic, mild, moderate, to severe infections,
resulting in ICU hospitalization and even death. In the US alone, there is a prediction of ~100,000 – 240,000
deaths from SARS-CoV-2 infections. There is an urgent need to 1) characterize the host innate and adaptive
response to SARS-CoV-2 and 2) to define immunologic biomarkers that can inform new approaches for
diagnostic, prognostic, therapeutic and preventative (e.g., vaccine) modalities in order to improve our ability to
treat and prevent disease.
To enhance the efficiency of immuophenotyping, the Precision Vaccines Program (PVP) has optimized a number
of sample-sparing in vitro assays to characterize both innate and adaptive immune function. These established
assays will be applied to the evaluation of SARS-CoV-2 infections and identification of biomarkers associated
with morbidity and mortality, which remains an unmet need and a research priority for the fight against COVID.
Through investigating soluble and cellular innate and adaptive immune mediators, we will gain insight into the
control of inflammation and infection in COVID. In Specific Aim 1 (SA1), we will measure, eg, (a) the plasma
enzyme adenosine deaminase (ADA) that metabolizes the anti-inflammatory metabolite adenosine to the
immunologically inert inosine, thereby enhancing Th1 immune responses and enhancing antiviral innate and
adaptive immunity; and (b) human defensins, antimicrobial peptides that enhance innate antiviral (e.g., IFN) and
neutralizing antibody (Ab) responses to coronaviruses. In SA2, we will employ system serology, to further
characterize Ab function and efficiency to SARS-CoV-2 across the severity of infection. In SA3, we will measure
responses of whole blood leukocytes to activation of pathogen recognition receptors (PRRs) as well as
responses of T-cell co-cultures to SARS-CoV-2 spike protein antigen.
Overall, successful completion of the proposed IMPACC Local Assay Site studies will provide unique insights
into human innate and adaptive immune responses to SARS-CoV-2 in relation to COVID progression and
prognosis. These insights will provide fresh approaches to develop diagnostics, therapeutics and preventative
measures against COVID-19, including vaccines.
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