# Pn3Pase as an Effective Enzyme Therapeutic for Streptococcus Pneumoniae type 3 Infection

> **NIH NIH R41** · PNEUMOTACTIX, LLC · 2022 · $299,450

## Abstract

Project Summary
Streptococcus pneumoniae (Spn) remains one of the deadliest infectious agents responsible for more than a
million deaths worldwide per year as well as making up a majority of secondary infections in
immunocompromised patients. One of the major virulence mechanisms associated with this pathogen is its
polysaccharide capsule, which determines successful colonization and infection of the bacterium as well as
serving as a defense mechanism against immune-mediated killing of the pathogen. Spn serotype 3 (Spn3) is
considered one of the most virulent serotypes of Spn, and despite current multivalent vaccines that include
conjugate targets against Spn3, the overall proportion of this serotype in Spn infection cases has actually
increased over the last ten years. Furthermore, Spn3 is directly associated with increased antibiotic resistance.
Thus, the severity of the impact of Spn3, as well as the difficulties arising in designing therapies against it, cannot
be overstated. Pneumozyme (Pn3Pase) is an enzyme product that we have previously shown to be highly
effective in degrading the capsular polysaccharide of type 3 Spn. Our in vitro studies have shown that treating
Spn3 with Pneumozyme will render the bacterium more susceptible to killing mechanisms by phagocytic cells.
Furthermore, mice that are lethally challenged with Spn3 can be rescued following treatment with Pneumozyme:
100% of mice receiving Pneumozyme treatment survival the challenge whereas 100% of mice that receive
inactive enzyme or vehicle die within two days of Spn3 lethal challenge. These results indicate that Pneumozyme
has extremely high efficacy in sensitizing Spn3 to host immune mechanisms and that the enzyme has remarkable
potential as a therapeutic. As part of Pneumotactix, LLC, our aims for this project are thus:
Aim 1: Characterize the pharmacokinetics, potential immunogenicity and cytotoxicity of the enzyme.
Aim 2: Elucidate the therapeutic value of the enzyme against Spn3 infection.
In our published studies, we have used the native, full-length protein product to degrade the capsule of one
virulent strain of Spn3 to great effect, and have further shown that this enzyme product does not induce cellular
toxicity against host mammalian cells in both in vitro and in vivo experiments. Our immediate goals for this
project are therefore to expand these studies to test pharmacokinetics, assess enzyme efficacy against
additional strains of serotype 3 Spn, and perform continued experiments to confirm the therapeutic value of
Pneumozyme and concurrent lack of off-target effects upon administration. The long-term goals for
Pneumozyme are to establish it as a therapeutic agent by testing its efficacy in higher animal systems (i.e.,
primates) with significant sample numbers of Spn type 3 clinical isolates, and move towards clinical trials to
develop this enzyme as a highly relevant therapeutic against this incredibly virulent pathogen.

## Key facts

- **NIH application ID:** 10448437
- **Project number:** 5R41AI157287-02
- **Recipient organization:** PNEUMOTACTIX, LLC
- **Principal Investigator:** Fikri Y Avci
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $299,450
- **Award type:** 5
- **Project period:** 2021-07-09 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10448437

## Citation

> US National Institutes of Health, RePORTER application 10448437, Pn3Pase as an Effective Enzyme Therapeutic for Streptococcus Pneumoniae type 3 Infection (5R41AI157287-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10448437. Licensed CC0.

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