BioNTech’s Engineered Endolysins for Bacterial Vaginosis Precision Phage Enzymes That Target Gardnerella

Bacterial vaginosis (BV) is the most common vaginal infection worldwide, affecting 10-40% of women depending on the population studied, and is associated with serious consequences including preterm labour, postpartum endometritis, and increased HIV transmission risk. A divisional patent from BioNTech SE describes novel recombinant endolysins – enzyme-based antibacterials derived from bacteriophages – engineered to selectively kill Gardnerella, the primary bacterial species driving BV pathology.

The Problem

BV occurs when the healthy Lactobacillus-dominated vaginal microbiome is displaced by a polymicrobial biofilm in which Gardnerella vaginalis is a key initiating species. Gardnerella was once considered a single species, but genomic analysis has revealed it to comprise at least 13 species, with Gardnerella vaginalis sensu stricto, Gardnerella piotii, and others playing roles in BV.

Current standard treatment relies on antibiotics such as metronidazole or clindamycin, which have several limitations. Antibiotic regimes treat the broad vaginal microbiome rather than specifically targeting Gardnerella, disrupting beneficial Lactobacillus populations in the process. Recurrence rates after antibiotic treatment are high: approximately 50-70% of patients experience BV recurrence within 6-12 months. Increasing antibiotic resistance is also a concern. There is a clear need for a species-selective treatment that can eliminate Gardnerella without disrupting the rest of the vaginal microbiome.

Endolysins are enzymes encoded by bacteriophages (viruses that infect bacteria) that lyse bacterial cell walls during the phage replication cycle. Recombinant endolysins applied externally can kill target bacteria with high specificity determined by the cell-wall binding domain, which recognises structures unique to specific bacterial species.

What This Invention Does

The patent describes recombinant domain-swapped endolysins engineered to kill Gardnerella species with high selectivity. The endolysins are constructed from domains derived from different natural endolysins, combining:

(i) a N-terminal catalytic domain (which performs the enzymatic lysis of the bacterial cell wall), from a first natural endolysin; (ii) a C-terminal cell-wall binding region containing at least one cell-wall binding domain (which determines the species specificity of the enzyme), from a second natural endolysin derived from a different prophage genome; and (iii) a linker region between the two domains, also from the second natural endolysin.

By swapping the catalytic and binding domains from different natural endolysins, the inventors have created hybrid enzymes with killing activity against Gardnerella that can be optimised for both lytic potency and species selectivity. The endolysins, polynucleotides encoding them, and pharmaceutical compositions containing them are described for use in treating bacterial infections, with BV as the primary indication. Local vaginal administration is the intended delivery route.

Key Features

Species-selective killing. The cell-wall binding domain determines bacterial species specificity, enabling the endolysins to target Gardnerella cells while leaving Lactobacillus and other beneficial vaginal bacteria unaffected – a fundamental advantage over broad-spectrum antibiotics.

Domain-swapped architecture. Recombinant fusion of catalytic and cell-wall binding domains from different prophage-encoded endolysins allows engineering of hybrid proteins with improved or novel killing activity not present in either parent endolysin alone.

Local vaginal delivery. The pharmaceutical composition is designed for local vaginal administration, maximising drug concentration at the site of infection while minimising systemic exposure.

Polynucleotide encoding. The invention also covers polynucleotides encoding the endolysins, enabling mRNA-based or gene therapy delivery approaches consistent with BioNTech’s broader therapeutic platform expertise.

Multiple Gardnerella species coverage. Given the recent recognition that Gardnerella comprises multiple species, the engineered endolysins are evaluated for killing activity across the relevant Gardnerella species associated with BV pathology.

Who Is Behind It?

The applicant is BioNTech SE of Germany. The sole named inventor is Lorenzo Corsini. This divisional was filed on 26 February 2026, derived from parent application AU 2020268752, which traces to PCT/EP2020/062645 (WO 2020/225335). Griffith Hack in Melbourne are the Australian patent attorneys.

Why It Matters

BV is a condition with substantial public health impact – it is the most prevalent vaginal condition globally – yet remains inadequately treated with available therapies. The high recurrence rate after standard antibiotic treatment reflects a fundamental limitation of broad-spectrum antibiotics in an environment where the healthy Lactobacillus microbiome needs to be preserved and encouraged to re-establish. A precision endolysin therapy that selectively eliminates the Gardnerella biofilm without harming Lactobacilli could provide more durable remission by preserving the competitive exclusion provided by a healthy vaginal microbiome.

BioNTech’s involvement in this field is notable. The company’s experience with mRNA-based therapeutics creates the possibility of delivering endolysin-encoding mRNA locally to the vaginal epithelium – a delivery modality that would be consistent with their broader platform and could offer advantages in terms of duration of activity and ease of production.

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AU 2026201469 was published in the Australian Official Journal of Patents on 19 March 2026 and is open for public inspection. Patent applications represent inventions that are sought to be protected and do not necessarily reflect commercially available products.

Related Concepts

Endolysins are enzymes encoded by bacteriophages that degrade bacterial cell walls with high specificity, determined by their cell-wall binding domains. Unlike broad-spectrum antibiotics such as metronidazole, engineered endolysins can be designed to selectively kill target pathogens while leaving beneficial bacteria like Lactobacillus intact – a critical advantage in polymicrobial environments such as the vaginal microbiome where preserving the healthy microbial community is essential to achieving durable treatment outcomes.