# Group A Streptococcus Vaccination to prevent Strep throat in an NHP model

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $158,000

## Abstract

Project Summary:
 There are currently no approved vaccines for Group A Streptococcus (GAS). GAS is a widespread
pediatric problem causing an estimated 616 million cases of strep throat each year worldwide. Untreated strep
throat can lead to serious autoimmune sequelae such as rheumatic heart disease (RHD) which inadvertently
develops out of molecular mimicry from the host immune response to GAS infection. RHD results from damaged
heart valves, claiming the lives of 288,000 people each year worldwide, per the World Health Organization.
Therefore there is a critical need for a GAS vaccine.
 We had first studied why some children get recurrent strep throat by studying the tonsillar germinal center
response in children who had undergone tonsillectomy for either recurrent strep tonsillitis or non-recurrent
tonsillitis. Tonsils are the lymphoid tissue which likely mount the first adaptive immune response to GAS. We
observed that children with recurrent strep throat had a deficit in circulating antibodies against a critical GAS
virulence factor streptococcus pyrogenic exotoxin A (SpeA). This was an interesting finding as there has been a
long clinical association demonstrating the protective nature of SpeA antibodies against the development of GAS
toxic shock syndrome. SpeA is a superantigen which is necessary to establish infection in a humanized mouse
model. We discovered that SpeA induced CD4+ T cells with the capacity to kill instead of help B cells within
germinal centers. We named these cells “killer T follicular helper (Tfh)” cells. We found that children with recurrent
strep throat had more SpeA induced “killer Tfh” cells and significantly smaller germinal centers, likely explaining
their propensity for recurrent strep infections. We hypothesize that an SpeA toxoid vaccination will protect against
GAS pharyngitis or tonsillitis by limiting the development of SpeA-induced “killer Tfh” cells and allowing for the
development of GAS-specific germinal center responses to quickly clear a GAS tonsillar infection. This proposal
focuses on evaluating whether an SpeA toxoid vaccine will prevent GAS tonsillitis and pharyngitis in a non-
human primate model and understanding the impact of SpeA toxoid vaccination in altering the GAS germinal
center response. The long term objective is to demonstrate the utility of GAS toxoid vaccinations in preventing
disease.

## Key facts

- **NIH application ID:** 10647875
- **Project number:** 5R21AI171385-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Jennifer Marie Dan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $158,000
- **Award type:** 5
- **Project period:** 2022-06-16 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10647875

## Citation

> US National Institutes of Health, RePORTER application 10647875, Group A Streptococcus Vaccination to prevent Strep throat in an NHP model (5R21AI171385-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10647875. Licensed CC0.

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