# Immunization against filamentous bacteriophages to prevent bacterial infection

> **NIH NIH R01** · UNIVERSITY OF MONTANA · 2022 · $962,774

## Abstract

Immunization against filamentous bacteriophages to prevent bacterial infection
 Pseudomonas aeruginosa (Pa) is a deadly pathogen and a major cause of infections in diabetic wounds
and other settings. Due to extensive antibiotic resistance, it is increasingly difficult to treat Pa infections once
they are established. It would be ideal to vaccinate diabetic patients against Pa before they develop infected
ulcers. However, there are no approved vaccines that prevent Pa infections. One major challenge is identifying
microbial targets that are amenable to immunization and common across all Pa strains and serotypes. Pf
bacteriophage (phage) are a novel virulence factor in Pa infections. Unlike most bacteriophage that parasitize
bacteria, Inoviruses like Pf do not typically lyse (kill) their bacterial hosts. Instead, Pf increases Pa fitness. We
recently reported that Pf phage increase bacterial aggregation and decrease motility of Pa—phenotypes that
facilitate initial colonization of wounds and other surfaces. In addition, Pf phage act as structural elements that
promote the formation and pathogenic functions of biofilms. Based on these results, we hypothesized that
immunization against Pf phage would protect against Pa infection. Our preliminary data indicate that immunity
against Pf phage is indeed protective against Pa infection. Using a peptide sequence from the major coat
protein (CoaB) of Pf as an antigen, we find that vaccination promotes opsonization and reduces Pa infection in
a mouse wound infection model. To develop Pf phage vaccination as a therapy, further proof-of-concept
studies are needed. The optimal adjuvant and vaccine formulation needs to be determined and the efficacy of
this vaccine needs to be demonstrated in physiologically relevant animal models of human wound infections.
The sensitivity and specificity of our vaccine against diverse Pa strains and serotypes also needs to be
demonstrated. In light of our striking preliminary data, we hypothesize that a vaccine against Pf phage will
protect against Pa wound infections. To test this hypothesis, we have established a team of microbiologists,
immunologists, and wound infection scientists and partnered with Inimmune, Corp., an industry leader in
vaccine development. In Aim 1, we will optimize our candidate vaccine that targets Pf phage to prevent Pa
infection. In Aim 2, we will demonstrate the efficacy of our vaccine in animal models of Pa wound infection. In
Aim 3, we will define the sensitivity and specificity of anti-Pf phage immunity against Pa clinical isolates.
Together, these aims represent a bold, imaginative, and radically unconventional approach to preventing Pa
wound infections. If successful, this work will give rise to the first vaccine against Pa and the first vaccine to
target a bacteriophage.

## Key facts

- **NIH application ID:** 10394946
- **Project number:** 5R01AI138981-05
- **Recipient organization:** UNIVERSITY OF MONTANA
- **Principal Investigator:** Jay T. Evans
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $962,774
- **Award type:** 5
- **Project period:** 2018-06-08 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10394946

## Citation

> US National Institutes of Health, RePORTER application 10394946, Immunization against filamentous bacteriophages to prevent bacterial infection (5R01AI138981-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10394946. Licensed CC0.

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