# Identifying the Most Effective Adjuvant(s) for Leading Group A Streptococcal Vaccine Antigens in Preclinical Mouse and Nonhuman Primate Models

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $658,644

## Abstract

SUMMARY
The leading human bacterial pathogen group A Streptococcus (GAS) causes over 700,000,000 cases of
superficial disease such as pharyngitis and pyoderma each year but can also lead to serious invasive infections
and autoimmune sequelae, which combine to make GAS one of top 10 causes of infection-associated deaths
worldwide. The highest mortality burden of GAS disease is caused by rheumatic heart disease (RHD), which
results from repeated bouts of acute rheumatic fever (ARF). It is difficult to overstate the urgent public health
need for a safe and efficacious GAS vaccine for human use. A significant number of experimental GAS vaccines
are backlogged in preclinical development, with questions around safety, global GAS strain coverage, potential
for efficacy in humans (i.e. lack of animal efficacy model data that accurately reflects disease). We have recently
demonstrated that choice of adjuvant plays a pivotal role in imparting protective efficacy for an experimental
multi-component GAS subunit vaccine in both a murine invasive disease model and the non-human primate
(NHP) model that closely recapitulates GAS pharyngitis, the primary target for vaccine protection. Moreover,
these studies suggest that promoting immunity skewed towards Th1 may elicits optimal protection beyond that
afforded by the standard Alum adjuvant formulation. Herein, our highly experienced team of scientists with an
extensive track record of productive collaboration will expand this important line of investigation to deliver proof-
of-concept of the impact of adjuvant on the efficacy of three leading experimental GAS vaccines: (1) a 30-valent
N-terminal M protein vaccine (StreptAnova) from the University of Tennessee that has reached phase 1 human
trials; (2) Vaxcyte VAX-AI from Vaxcyte, Inc. in collaboration with UC San Diego, a conjugate vaccine with
modified group A carbohydrate conjugate, and GAS proteins SLO, SpyAD, SCPA; and (3) Combo#5 from the
University of Queensland incorporating 5 conserved immunogenic GAS antigens: SLO, SCPA, SpyCEP, ADI,
TF. The vaccines will be formulated with Alum or selected emulsion and liposome-based adjuvants, using four
distinct mouse models (skin, intranasal, intraperitoneal and invasive disease). Protective efficacy, immune
response, correlates of protection, and vaccine safety (cross reactivity to human heart tissue) will be assessed.
Finally, protection afforded by three selected vaccine-adjuvant combinations will be assessed in the non-human
primate model of GAS pharyngitis, which most closely mimics GAS primary infection of humans, and clinical
scoring and vaccine safety parameters determined. To advance the entire GAS vaccine field, our head-to-head
comparison of M protein and non-M protein GAS vaccines, in both select mouse models and the NHP pharyngitis
model, will have broad implications. across the field. We will identify the most efficacious antigen and adjuvant
formulations using the animal models we have developed. Adju...

## Key facts

- **NIH application ID:** 10760289
- **Project number:** 5R01AI173689-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Victor Nizet
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $658,644
- **Award type:** 5
- **Project period:** 2023-01-05 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10760289

## Citation

> US National Institutes of Health, RePORTER application 10760289, Identifying the Most Effective Adjuvant(s) for Leading Group A Streptococcal Vaccine Antigens in Preclinical Mouse and Nonhuman Primate Models (5R01AI173689-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10760289. Licensed CC0.

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