# Regulation of germinal center responses by SARS-CoV-2 messenger RNA vaccines

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2022 · $660,497

## Abstract

SUMMARY
Messenger RNA (mRNA) vaccines represent a powerful vaccine approach for the induction of protective immune
responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since this vaccine platform
was approved for human use in 2020 for the first time, little is known about the durability and mechanisms of
induction of the immune responses elicited by SARS-CoV-2 mRNA vaccines. In mice, the generation of SARS-
CoV-2 neutralizing antibodies (nAbs) driven by mRNA vaccines is associated with the formation of robust
germinal centers (GCs). GCs are sophisticated processes during which antigen-specific B cells give rise to high-
affinity Ab-secreting cells and memory B cells. The GC reaction is tightly regulated by T follicular helper (Tfh)
cells, which are also efficiently generated during SARS-CoV-2 mRNA vaccination. In this grant proposal, we
seek to address the following 3 fundamental questions related to SARS-CoV-2 mRNA vaccines: 1) How durable
are the GC-derived B cell responses to SARS-CoV-2 mRNA vaccines in mice and humans?; 2) What types of
antigen presenting cells (APCs) promote Tfh cell differentiation in SARS-CoV-2 mRNA vaccination? And how
do these APCs sense these mRNA vaccines?; and 3) How do SARS-CoV-2 mRNA vaccines induce GC B cell
responses? Overall, the studies that we propose here will allow us to determine the longevity of GC-derived B
cell responses and to shed light on the mechanisms by which SARS-CoV-2 mRNA vaccines ensure a powerful
elicitation of Tfh and GC B cells. The knowledge acquired here will be important to inform future boosting
strategies for SARS-CoV-2 mRNA vaccination, as well as the rational design of next generation vaccines for
difficult-to-neutralize pathogens.

## Key facts

- **NIH application ID:** 10423258
- **Project number:** 1R01AI168312-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Michela Locci
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $660,497
- **Award type:** 1
- **Project period:** 2022-02-09 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10423258

## Citation

> US National Institutes of Health, RePORTER application 10423258, Regulation of germinal center responses by SARS-CoV-2 messenger RNA vaccines (1R01AI168312-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10423258. Licensed CC0.

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