# Interrogating human anti-staphylococcal antibody responses for S. aureus vaccine insights

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $813,730

## Abstract

Abstract
Staphylococcus aureus is a leading cause of infection worldwide and a major driver of antibiotic
resistance. Although many experimental staphylococcal vaccines have been reported, all vaccines
tested to date in human trials have failed for unclear reasons. Unlike mice, humans are exposed to S.
aureus beginning early in life, leading to generation of antibodies to S. aureus antigens. In preliminary
experiments, we have shown that select human anti-S. aureus antibodies are protective, but many are
not. In mice exposed to S. aureus, vaccination against protective antigens leads to immunity against S.
aureus whereas vaccination against non-protective antigens induced recall of non-protective immunity
which further interferes with protective antibodies by direct competition. Based on these findings, we
generated a model of how pre-existing antibodies shape vaccine responses and how this predicts novel
ways to develop effective vaccines against S. aureus. To query the validity of our model, in Aim 1, we
will recruit children and old adults with invasive S. aureus infections, survey the anti-S. aureus antibody
profile and define functionally protective antibody responses to S. aureus antigens. In Aim 2, we will
identify and characterize protective and non-protective anti-S. aureus antibodies from candidate
samples acquired in Aim 1, and assess structural and functional features of the specific antibodies that
confer protection or non-protection. In Aim 3, we will study these antibodies and their target in the
context of naïve mice and mice previously exposed to S. aureus. We will evaluate mechanisms
whereby non-protective memory shapes vaccine efficacy and test strategies that circumvent
interference. Overall, using the novel model systems, we aim to develop a more predictive framework
for explaining staphylococcal vaccine failures and developing novel strategies for effective vaccination
against S. aureus.

## Key facts

- **NIH application ID:** 10933027
- **Project number:** 5R01AI181321-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Clarence Buddy Creech
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $813,730
- **Award type:** 5
- **Project period:** 2023-09-20 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10933027

## Citation

> US National Institutes of Health, RePORTER application 10933027, Interrogating human anti-staphylococcal antibody responses for S. aureus vaccine insights (5R01AI181321-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10933027. Licensed CC0.

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