# Overcoming pathogen-mediated immune evasion: a translational approach to pediatric Staphylococcus aureus vaccine development - Resubmission 01

> **NIH NIH R01** · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · 2020 · $380,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Preventing infections caused by Staphylococcus aureus is a public health imperative, but there is currently no
effective vaccine. Clinical trials for S. aureus vaccines and immunotherapeutics have focused on preventing
infection in adults with a particularly high burden of S. aureus infections, but no efforts have been made to
challenge the existing dogma and develop an immunization strategy that will afford early and broad population-
based protection. We hypothesize that seemingly benign exposures to S. aureus in early childhood pattern
deleterious immune responses, effectively “trapping” the immune system, a concept introduced by Francis as
“original antigenic sin”. Therefore, we predict that a successful S. aureus vaccine will require an alternative,
highly mechanistic approach to vaccine design with the goal of overdriving original antigen sin, and
implementation in the pediatric population to deliberately drive the host immune response toward a protective
phenotype prior to the establishment of natural suboptimal responses.
The studies in this proposal will test this hypothesis using tractable animal models of S. aureus infection and
clinical studies in healthy and S. aureus–infected children. Taking advantage of the convergence of natural
and vaccine-elicited immunity in our mouse model, we will use a novel vaccine and newly synthesized peptide
MHC (pMHC) tetramers as tools to precisely define the mechanisms by which synergistic antibody and T cell
responses impact local inflammatory responses and bacterial outgrowth at the tissue level. A mechanistic
approach to overdrive infection-patterned immunity in the mouse model will be complemented by a targeted
investigation in healthy and S. aureus-infected children to determine the onset and impact of patterned
immunity. This clinicotranslational approach is anticipated to lay the foundation for future vaccine trials in the
pediatric population.

## Key facts

- **NIH application ID:** 9979738
- **Project number:** 5R01AI125489-04
- **Recipient organization:** RESEARCH INST NATIONWIDE CHILDREN'S HOSP
- **Principal Investigator:** Christopher Montgomery
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $380,000
- **Award type:** 5
- **Project period:** 2017-08-08 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979738

## Citation

> US National Institutes of Health, RePORTER application 9979738, Overcoming pathogen-mediated immune evasion: a translational approach to pediatric Staphylococcus aureus vaccine development - Resubmission 01 (5R01AI125489-04). Retrieved via AI Analytics 2026-06-03 from https://api.ai-analytics.org/grant/nih/9979738. Licensed CC0.

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