# Immunogenetics of COVID-19 Immune Response

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2024 · $814,873

## Abstract

PROJECT SUMMARY/ABSTRACT
This application is a request for funding of a vaccine immunogenetics research program focused on identifying
critical genetic and phenotypic determinants of COVID-19 infection and/or vaccination-induced immunity by
examining associations between gene polymorphisms, HLA allelic variation, and clinical phenotypes and inter-
individual variations in immune response to COVID-19. Our laboratory has done significant work delineating
the effect of gene polymorphisms on mumps, measles, rubella, influenza, and smallpox vaccine immune
responses. Our research demonstrates that variations in immune responses to viral vaccines are multigenic
and not a single dominant allele model and that the genetic contribution to such variations in immune
responses can be quantified. Informed by insights from these studies and given the public health importance of
the ongoing SARS-CoV-2 pandemic, we now turn our attention to understanding genetic associations with
COVID-19-induced immune responses (regardless of whether they are vaccine or infection-induced, or a result
of hybrid immunity). The most thorough and efficient study for such purposes is a comprehensive
discovery/replication genome-wide association study (GWAS), to which we will add a phenome association
study (PheWAS) followed by a more complete characterization of distinct immune effector mechanisms
believed to contribute to protective immunity. Our studies will identify gene polymorphisms and pathways
having the largest or most critical impact on inter-individual variations in immunity among subjects, and how
comorbidities (phenotypes) contribute to these variations. Our Specific Aims are to 1) perform a large,
genome-wide association study to identify novel genetic associations between SNPs and HLA alleles and
inter-individual variations in the humoral immune response to COVID-19 infection or vaccination; identify
polygenic risk scores predictive of antibody response; replicate the findings in an independent cohort; evaluate
significant findings in a cohort with documented infection and no vaccination; 2) conduct a phenome-wide
association study to quantify the effect of additional subject characteristics (e.g., age, sex, race, ethnicity,
BMI), comorbidities, and phecodes (clusters of ICD10 codes) on the antibody response to COVID-19 vaccines;
and 3) Evaluate the effect of genetic variation and host factors on T cell and B cell markers of immune
response following vaccination. These aims will allow us to comprehensively define how inter-individual
variations in immune responses to COVID-19 vaccine are influenced by gene polymorphisms and host
characteristics. Notably, despite the public health implications, there are no population-based studies
identifying associations between COVID-19 vaccine immune response and genome-wide SNPs or clinical
phenotypes. Our study is carefully designed to be rigorous and produce robust, unbiased, and reproducible
results applicable to the US populati...

## Key facts

- **NIH application ID:** 10988035
- **Project number:** 1R01AI179709-01A1
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Richard B Kennedy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $814,873
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10988035

## Citation

> US National Institutes of Health, RePORTER application 10988035, Immunogenetics of COVID-19 Immune Response (1R01AI179709-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10988035. Licensed CC0.

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