Recent groundbreaking research from the University of Cincinnati reveals the potential of engineered bacteria, specifically E. coli Nissle 1917, as a novel platform for delivering antiviral therapies and vaccines. The study, led by Dr. Nalinikanth Kotagiri, has been published in the journal Gut Microbes, highlighting the important implications for mucosal immunization and therapy against viruses such as SARS-CoV-2.

Advancing Antiviral Therapies

The innovative use of engineered bacteria represents a paradigm shift in how antiviral treatments can be administered. Traditional methods often require needles and complex cold-chain logistics; however, the oral delivery system proposed in this research offers a more accessible and efficient method. The bacterium is designed to release therapeutic payloads directly to the gastrointestinal tract, a key entry point for many viruses.

Dr. Kotagiri stated, "Oral delivery lets us target the mucosal surfaces where pathogens first gain a foothold," emphasizing the advantages of this method over conventional approaches.

Vaccine Delivery Improvements

Unlike most engineered bacteria that retain their therapeutic agents within the cell, this new approach utilizes outer-membrane vesicles (OMVs) generated by the bacteria. These OMVs act as self-propelled carriers, effectively transporting their contents through the gut epithelium into the bloodstream, thereby enhancing the systemic and mucosal immune responses.

The research team focused on presenting viral antigens, specifically the spike protein of the SARS-CoV-2 virus, on the surface of the engineered E. coli. This achieved results comparable to those of traditional mRNA vaccines, indicating that:

  • The two-dose oral regimen led to systemic antibody levels similar to those achieved with intramuscular injections.
  • Significantly increased levels of secretory immunoglobulin A (IgA) were observed in the gut, which is crucial for blocking infections.

Therapeutic Applications

In addition to vaccine applications, the researchers have developed a prototype for post-exposure therapy. This version also utilizes engineered E. coli to produce therapeutic proteins that can neutralize viruses after infection.

  • One such development involves coding anti-spike nanobodies into the bacteria, which, upon release, effectively accumulated in lung tissue and neutralized SARS-CoV-2 in ex-vivo assays.
  • By utilizing OMVs for delivery, these nanobodies can be concentrated and directed to their targets with high efficiency.

Safety and Future Directions

The engineered bacteria have exhibited a favorable safety profile in animal models, without inducing adverse immune responses or side effects. With the foundational strain having decades of safe use as a probiotic, this new application for viral therapies appears promising.

Looking ahead, Dr. Kotagiri envisions rapid adaptability of this platform for other viral targets, such as influenza and norovirus. He stated, "All that optimization was necessary for us to prove that this is a platform that we can take forward," indicating robust future research trajectories.

Potential Applications and Clinical Trials

The potential for this technology extends beyond SARS-CoV-2. The development of integrated systems that combine both vaccination and therapy within the same bacterial construct could revolutionize treatment modalities.

Research Focus Anticipated Outcome
Oral Delivery System Targeted mucosal immune response
OMV Utilization Improved delivery efficiency of therapeutic agents
Nanobodies Integration Post-infection therapeutic efficacy

Clinical trials will be critical to validate the system's safety and efficacy. Early indications suggest that the engineered bacteria have significant potential for enhancing the body's defenses against viral infections.

Conclusion

The work conducted by Dr. Kotagiri and his team at the University of Cincinnati heralds a new chapter in the development of antiviral therapies and vaccines. By leveraging engineered probiotic bacteria, researchers are paving the way for innovative, accessible, and effective means of combating viral threats.

More information: Nitin S. Kamble et al, Engineered bacteria as an orally administered anti-viral treatment and immunization system, Gut Microbes (2025). DOI: 10.1080/19490976.2025.2500056