# Integrated Analysis of SARS-CoV-2 Vaccine Responses During Aging

> **NIH NIH R21** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $255,860

## Abstract

Production of high-affinity class-switched antibodies is essential for elimination of viruses and immunity elicited
by vaccination. Vaccination has led to the eradication of some diseases, but in some settings do not provide
sufficient protection, such as in elderly or immunocompromised individuals. Antibody responses are controlled
by humoral immunoregulatory pathways, including inhibition by Tfr cells, which suppress B cell effector functions.
Aged-related defects in vaccine responses are partially due to enhanced humoral immunoregulation by Tfr cells.
Since the COVID19 pandemic disproportionally affects at-risk populations such as the elderly, new vaccine
strategies need to be developed to enhance protection for this group. However, a fundamental understanding
of how humoral immunoregulation associated with aging alters SARS-CoV-2 vaccine responses is lacking. We
hypothesize that augmented humoral immunoregulation by Tfr cells during aging alters SARS-CoV-2 vaccine
responses, and that limiting Tfr cells can enhance vaccine efficacy. We also hypothesize that limiting humoral
immunoregulation results in production of new and unique therapeutic antibodies. To test these hypotheses, we
will use a novel systems-based approach to integrate, on a per cell basis, SARS-CoV-2 antibody specificity,
breadth, viral neutralization potential, and antibody sequence/clonality. We will use novel Tfr-deleter mice to
assess how humoral immunoregulation alters these responses. Our aims are to 1) determine how augmented
humoral immunoregulation in aging alters clonal selection of neutralizing antibodies during SARS-CoV-2
vaccination, and 2) determine how eliminating humoral immunoregulation enhances clonal selection of
neutralizing antibodies. Our goals are to determine, in detail, how humoral immunoregulation alters antibody
selection to control effector antibody responses after vaccination.

## Key facts

- **NIH application ID:** 10175583
- **Project number:** 1R21AI158175-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Peter The Sage
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $255,860
- **Award type:** 1
- **Project period:** 2021-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10175583

## Citation

> US National Institutes of Health, RePORTER application 10175583, Integrated Analysis of SARS-CoV-2 Vaccine Responses During Aging (1R21AI158175-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10175583. Licensed CC0.

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