Streptococcus preparation for treatment of respiratory tract infections
A next-generation probiotic therapy using human nasal bacteria and their antimicrobial peptides to block pneumococcal colonisation, preventing infection and transmission at its source.
BACKGROUND
Streptococcus pneumoniae (pneumococcus) is a major cause of pneumonia, otitis media, and sinusitis worldwide affecting mainly children, the elderly and immunocompromised individuals despite widespread use of antibiotics and conjugate vaccines. Current pneumococcal conjugate vaccines are highly effective but cover only up to 21 of more than 100 known serotypes. Long‑term surveillance has shown clear serotype replacement, with non‑vaccine serotypes increasingly responsible for disease. In parallel, the global rise of multidrug‑resistant pneumococcal strains is eroding the effectiveness of standard antimicrobial therapies, while antibiotic use itself perturbs the microbiota and drives broad selective pressure for resistance.
These converging limitations have created a clear need for alternative and complementary approaches that prevent pneumococcal infection. Pneumococcal colonization of the upper respiratory tract, which occurs as a biofilm, is common and is a necessary first step for both disease and transmission. Recognizing this, the World Health Organization now recommends that new interventions to reduce pneumococcal disease should also target colonization rather than focusing solely on treatment/prevention of established infections.
One promising concept is the use of bacterial strains with probiotic traits and their antimicrobial peptides as targeted therapeutics that inhibit pathogens, a strategy already being tested in other infection contexts such as gut and skin infections. Our work evaluated the use of such strategies to specifically suppress pneumococcal colonization. We did a systematic screening of human commensal streptococci that share the same upper‑respiratory niche as S. pneumoniae. We identified seven bacterial strains with strong anti‑pneumococcal activity due to the production of antimicrobial peptides. This approach is a new alternative to prevent colonization, disease and transmission.
TECHNOLOGY OVERVIEW
The invention is built around seven human upper‑respiratory commensal isolates: one S. oralis (A22) and six S. mitis (B22-G22) strains selected from over 300 non‑pneumococcal streptococci. These isolates were collected from the upper respiratory tract of healthy children and adults not colonized with S. pneumoniae and with no recent antibiotic use at the time of sampling. The seven commensals A22-G22 were screened in overlay assays against over 200 genetically diverse pneumococcal strains (spanning 30 serotypes and 157 MLST types). Strains A22 to G22 were chosen because each strain inhibits more than 90% of this diverse pneumococcal panel.
Whole‑genome sequencing of strains A22 to G22 revealed 64 bacteriocin‑related loci encoding 70 putative bacteriocins and 119 immunity proteins, including bacteriocin-like peptide (blp), competence‑associated (cab), streptococcin (lactococcin‑972‑like), and lantibiotic loci, many of which are absent or rare in over 7,000 S. pneumoniae genomes. Deletion of bacteriocin loci showed that several are required for the anti-pneumococcal inhibitory activity of the commensal strains.
In vitro, these strains, individually and as a cocktail, prevent formation of, and disrupt established, S. pneumoniae biofilms. As of yet, the inhibitory activity of strain F22 has been evaluated in vivo using a modified mouse model of S. pneumoniae and influenza A virus co-infection, and shown to prevent S. pneumoniae progression to the lungs. Moreover, treatment with bacteriocins Bac1, Bac2 and BlpOlike2 produced in vitro were shown to decrease S. pneumoniae colonization in a mouse model of nasopharyngeal colonization.
Figure 1: S. mitis F22 s a live biotherapeutic that blocks colonization and lung invasion.
BENEFITS AND APPLICATIONS
This technology can generate value across several sectors, including human vaccines and biologics, microbiome‑based therapeutics, pediatric and respiratory health, and anti‑infective drug discovery. In the vaccine and respiratory space, it provides a way to reduce pneumococcal colonization and thereby complement existing conjugate vaccines, particularly for non‑vaccine serotypes that are increasingly implicated in disease due to serotype replacement. In the microbiome and live biotherapeutic field, it offers human‑derived commensal strains and peptides that inhibit S. pneumoniae in a targeted way, avoiding the broad microbiota disruption and resistance selection.
For pediatric and ear, nose and throat indications, such as recurrent otitis media and sinusitis, the ability of these strains to prevent formation and to disrupt established pneumococcal biofilms suggests a route to decrease the reservoir of carriage that underlies recurrent infections. In parallel, the extensive and mostly unique repertoire of bacteriocins encoded by these strains creates a discovery platform for new, narrow‑spectrum antimicrobials or engineered probiotic chassis tailored to S. pneumoniae. Compared with competing approaches, this solution combines broad activity against epidemiologically diverse pneumococcal isolates, mechanistically validated inhibition via multiple bacteriocin loci, and strong potential for multi‑strain cocktails, which together reduce the risk of resistance and align directly with WHO recommendations to target colonization as a key step in preventing pneumococcal disease and transmission.
INTELLECTUAL PROPERTY
Provisional patent application: Sá-Leão, R., Valente, C., Handem, S., Ferreira, B., Candeias, C., Borralho, J., Lança, J.
No. of application: PT119647
Date of submission: 09.08.2024
Applicant: Universidade Nova de Lisboa
Provisional title: Streptococcus Preparation for Treatment of Respiratory Tract Infection
PCT application no. PCT/EP2025/072499, filed 05.08.2025
OPPORTUNITY
We are open to several complementary forms of collaboration around this technology. At the translational level, we seek development and commercial partners with expertise in respiratory therapeutics or microbiome‑based products to co‑develop intranasal or oral live biotherapeutic formulations and to integrate these strains into existing respiratory or paediatric portfolios. Licensing opportunities are available for access to the strain collection, associated bacteriocin loci and know‑how, either for defined indications (e.g., pneumococcal colonization, recurrent otitis media) or broader respiratory disease prevention programs. In parallel, we are seeking investment to expand IP, perform safety and in vivo efficacy studies, and progress toward first‑in‑human trials.
NOVA Inventors
Raquel Sá-Leão
Carina Valente
Sara Handem
Catarina Candeias
João Borralho
João Lança
Bárbara Ferreira