# Host-driven antibody responses against Staphylococcus aureus

> **NIH NIH R21** · UNIVERSITY OF CHICAGO · 2024 · $246,000

## Abstract

ABSTRACT
Staphylococcus aureus is a human-adapted pathogen that replicates by asymptomatically colonizing its host.
S. aureus is also the causative agent of purulent skin and soft tissue infections as well as bloodstream
infections that result in the metastatic seeding of abscess lesions in all organ tissues. A hallmark of infection
and colonization is recurrence, a phenomenon that reflects both a failure of the host to generate protective
immunity and the highly versatile capacity of this pathogen to surmount innate and adaptive immune defenses.
As a consequence, approaches to identify the protective antigens of S. aureus to develop a successful vaccine
have failed, leading to the notion that staphylococcal-neutralizing adaptive responses may not be sufficient to
reduce burdens imposed by this pathogen. Here, we find that this might not always be the case.
Mice lacking
functional H2-O (the equivalent of human HLA-DO) inoculated with a mouse-adapted strain of S. aureus
efficiently de-colonized the pathogen. De-colonized mice resisted bloodstream challenge with the MRSA
isolate USA300 suggesting that they were immune to the pathogen. We found that T-cell dependent B cell
responses were required to control
S. aureus colonization in H2-O-deficient mice and that H2-O-deicient mice
produced higher titer S. aureus-specific antibodies compared to wild-type mice. H2-O is a negative regulator of
MHC-II peptide loading and presentation and was shown to restrict the loading of high affinity peptides. Thus,
we hypothesize that the muted immune responses against S. aureus are derepressed in mice lacking H2-O.
We propose to exploit this observation and identify S. aureus-immunodominant antigens and -specific T cells
and B cells as well as antibody sub-classes that lead to decolonization of the pathogen.

## Key facts

- **NIH application ID:** 10986215
- **Project number:** 1R21AI181332-01A1
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Tatyana V Golovkina
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $246,000
- **Award type:** 1
- **Project period:** 2024-07-12 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10986215

## Citation

> US National Institutes of Health, RePORTER application 10986215, Host-driven antibody responses against Staphylococcus aureus (1R21AI181332-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10986215. Licensed CC0.

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