# Biomaterials-based Immunoengineering for Periprosthetic Joint Infection

> **NIH NIH K08** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $177,404

## Abstract

Project Summary / Abstract
 Due to advances in biomedical engineering and medicine, joint replacement has restored function
and relieved pain for millions of people. However, subsequent infection of implanted joints (known as
periprosthetic joint infection or PJI) is a debilitating condition that can lead to multiple surgeries, long courses of
intravenous antibiotics, and/or loss of limb or even life. Staphylococcus aureus is one of the most common and
virulent organisms that causes PJI. S. aureus is also associated with significant morbidity and frequent relapse
following treatment. Vaccination against S. aureus is a promising strategy to prevent periprosthetic joint
infection. However, traditional vaccine systems designed to prevent S. aureus infection have failed in clinical
trials. The goal of this proposal is to evaluate a novel approach to immunotherapy for S. aureus PJI by
engineering a biomaterials-based vaccine platform (BiVAX). BiVAX is an injectable biodegradable scaffold that
elutes cytokines to recruit dendritic cells, contains adjuvant for activation, and is loaded with antigen at high
concentration for uptake by recruited cells. Our group has previously demonstrated that by using bacterial lysate
enriched for glycans as antigen in this biomaterials-based vaccine system, BiVAX is effective against preventing
S. aureus abscesses and lethality from sepsis due to different gram-negative species in mouse models. PJI is a
more challenging biofilm-associated device infection, and it is unknown if vaccination can prevent disease. In
this proposal, I will evaluate the effects of infection and vaccination on the host immune response and determine
the efficacy of BiVAX for preventing PJI in a well-characterized murine model of disease. I will determine murine
immune responses to PJI as a function of host immunity and pathogen virulence in Aim 1 and evaluate the effect
of BiVAX against PJI and compare its efficacy to traditional vaccination strategies in Aim 2.
 I am supported in these efforts by world experts in immunotherapy, vaccine science, and PJI including:
primary mentor David Mooney (immunoengineering); co-mentor Ruanne Barnabas (vaccine science),
collaborator David Scadden (stem cell biology/immunology); collaborator Jean Lee (murine S. aureus
vaccination); collaborator Michael Super (immunology and glycobiology); advisor Antonia Chen (arthroplasty and
human clinical trials for S. aureus vaccines); advisor Sandra Nelson (clinical periprosthetic joint infection); and
advisor Hang Lee (biostatistics). The resource-rich ecosystem of Massachusetts General Hospital, Harvard
University, and the Wyss Institute for Biologically Inspired Engineering have afforded me the necessary tools to
conduct this multidisciplinary work at the interface of bioengineering, microbiology, and immunology. This
proposal includes a robust training plan designed with my mentors to acquire additional skills in
immunoengineering and vaccine science necessary for la...

## Key facts

- **NIH application ID:** 11222203
- **Project number:** 7K08AI180362-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Alexander Mitchell Tatara
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $177,404
- **Award type:** 7
- **Project period:** 2024-06-14 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11222203

## Citation

> US National Institutes of Health, RePORTER application 11222203, Biomaterials-based Immunoengineering for Periprosthetic Joint Infection (7K08AI180362-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11222203. Licensed CC0.

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