# Staphylococcus aureus interference with IsdB vaccination

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $572,061

## Abstract

ABSTRACT
Staphylococcus aureus is a leading cause of infection worldwide and a major driver of antibiotic resistance.
Although many staphylococcal vaccines have been developed, all vaccines tested to date in human trials have
failed for unclear reasons. Unlike humans who are infected or colonized with S. aureus at an early age,
laboratory animals are rarely exposed to the human pathogen. Therefore, we queried if prior S. aureus
exposure, in the form of infection, modifies protective immunity conferred by IsdB vaccination. Strikingly, prior
staphylococcal infection in mice interferes with the induction of anti-staphylococcal immunity by IsdB
vaccination. The mechanism appears to be driven by IL-10 and S. aureus-experienced B cells. These findings
led us to hypothesize that S. aureus infection induces an ineffective B cell response associated with IL-10 that
is preferentially recalled when subsequent IsdB vaccine is administered (original antigenic sin). To address
our hypothesis, in Aim 1, we will determine how S. aureus- activated B cells and IL-10 modulate the host
immune response to IsdB vaccine and nullify anti-staphylococcal protection. In Aim 2, we will determine what
modifications to the IsdB-specific antibodies, induced by prior S. aureus exposure, make the antibodies non-
protective. In Aim 3, we will determine the broader clinical relevance of our findings by testing if vaccine
interference occurs in humanized BLT mice and in various clinically relevant settings.

## Key facts

- **NIH application ID:** 10696958
- **Project number:** 5R01AI144694-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** George Y Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $572,061
- **Award type:** 5
- **Project period:** 2019-09-18 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10696958

## Citation

> US National Institutes of Health, RePORTER application 10696958, Staphylococcus aureus interference with IsdB vaccination (5R01AI144694-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10696958. Licensed CC0.

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