Engineered bacteria can deliver antiviral therapies and vaccines

New research from the University of Cincinnati demonstrates how specially engineered bacteria taken orally can operate as a delivery system for antiviral therapies and vaccines. The research, led by Nalinikanth Kotagiri, Ph.D., is published in the journal Gut Microbes.

Kotagiri's lab focuses on engineering probiotic bacteria to accomplish a wide variety of functions, from breaking down cancer's defenses to imaging and diagnosing lung infections.

For the vaccine version, the bacteria E. coli Nissle 1917 was designed to express the spike protein found on the surface of the virus that causes COVID-19. This same spike protein is currently delivered through mRNA COVID-19 vaccines. In preclinical animal studies, a two-dose oral regimen generated blood-borne (systemic) antibody levels comparable to intramuscular mRNA vaccination.

The team also developed another version of engineered E. coli Nissle 1917 to display therapeutic proteins on the surface. To create a post-exposure therapy, the team encoded anti-spike nanobodies: antibodies that are one-tenth the size of conventional monoclonal antibodies.

Although full viral-challenge studies are pending, nanobodies released from the engineered bacteria reached the bloodstream, likely facilitated by OMVs, and accumulated in lung tissue, where they neutralized SARS-CoV-2 in ex-vivo assays.

Image source: Kamble et al. (2025), Gut Microbes.