Researchers have produced vaccine-like immune responses to a dangerous bacterium by colonizing 26 healthy volunteers with a related, but harmless, commensal bacterial species. The first-in-human, controlled infection study showed the strategy was safe, as no side effects were reported and the volunteers didn't transmit the commensal bacteria to bedroom-sharers over the 90-day study.
Neisseria lactamica is a member of the microbiome that usually resides in the upper airways of children but can also safely colonize the airways of adults.
Some researchers theorize that these bacteria could serve as vehicles for immunization, by delivering molecules from more dangerous bacteria to the respiratory system. But commensal bacteria are usually tolerated by the immune system, and it has been difficult to genetically engineer N. lactamica to deliver bacterial antigens.
However, Jay Laver and colleagues successfully engineered N. lactamica to express Neisseria Adhesin A as a vaccine antigen. Neisseria Adhesin A is a protein from a related species named Neisseria meningitidis, which can cause meningitis.
The team intranasally inoculated 26 adult volunteers with the engineered N. lactamica, which persisted in 86% of the subjects for 90 days. The colonization produced immune responses against Neisseria Adhesin A from both plasma cells and memory B cells within 28 days, and the B cells persisted for at least 90 days after colonization.
There were no adverse effects in the volunteers, none of them transmitted the N. lactamica to any contacts who shared the same bed, and the bacteria could be eradicated after 90 days with antibiotics. Laver et al. conclude their delivery system could be used in other applications, such as manipulating the respiratory microbiome or inducing immune tolerance to allergens.
Laver, J. R., et al. (2021) A recombinant commensal bacteria elicits heterologous antigen-specific immune responses during pharyngeal carriage. Science Translational Medicine. doi.org/10.1126/scitranslmed.abe8573.