# Systems biological assessment of T cell responses to vaccination

> **NIH NIH U19** · STANFORD UNIVERSITY · 2022 · $309,746

## Abstract

ABSTRACT – Project 2
The goal of Project 2 is to assess T cell responses in the context of proposed studies of: (i) COVID-19
vaccines that utilize novel platforms (mRNA) or adjuvants (Matrix M used in the Novavax vaccine) and (ii)
Humans given broad spectrum antibiotics that disrupt their microbiome, prior to and during rabies vaccination.
This goal is highly synergistic with those of Projects 1 and 3, which will evaluate innate and B cell responses
respectively, in the context of the same clinical trials. We will use new developed state-of-the-art techniques
that will allow us to probe the vaccine responses here with an unprecedented scale and depth. The three
methods are: (1) spheromer probes for specific T cells, (2) GLIPH (for Grouping of Lymphocyte Interactions by
Paratope Hotspots) analysis of TCR specificity groups, and (3) immune organoids. We will apply these tools in
the following aims:
Aim 1: Assessment of T cell responses to vaccination against COVID-19.
Sub-aim 1a. Analyze T cell responses induced by the BNT162b2 mRNA vaccine in healthy versus atopic
individuals. We will use the spheromer technology mentioned above, to create and use a panel of pMHC
Spheromers SARS-CoV-2 spike epitopes covering the major class I and II HLA alleles, to analyze the T cell
response, in healthy versus atopic subjects. In addition, we will perform TCR repertoire analysis using GLIPH2
to analyze both bulk and single cell TCR sequences in order to define the frequency, phenotype, function and
TCR diversity of antigen specific T cell responses to primary and secondary vaccination in blood and the
draining lymph nodes of both healthy adults and allergy prone subjects.
Sub-aim 1b: Assessment of T cell responses induced by the Novavax Matrix-M adjuvanted subunit vaccine.
We will also analyze samples collected from a Novavax sponsored trial done at the University of Witwatersrand
with spheromers and TCR sequence analysis and determine how the response to an adjuvanted subunit
vaccine differs from that induced by mRNA vaccination
Aim 2: Assessment of the impact of the microbiota on the antigen-specific T cell response to
vaccination. We will assess the impact of broad-spectrum antibiotics on the primary T cell response to rabies
vaccination. In particular, we will analyze the TCR repertoire and phenotype of T cells responding to this
vaccine, since there are clear indications that the microbiome can influence T cell phenotype, and we
hypothesize that there might be an influence on the repertoire as well.

## Key facts

- **NIH application ID:** 10419280
- **Project number:** 1U19AI167903-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Mark Morris Davis
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $309,746
- **Award type:** 1
- **Project period:** 2022-03-07 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10419280

## Citation

> US National Institutes of Health, RePORTER application 10419280, Systems biological assessment of T cell responses to vaccination (1U19AI167903-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10419280. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*