Engineered Bacteria Delivered via Nosedrops Provokes Immune Response Against Meningitis

Engineered Bacteria Delivered via Nosedrops Provokes Immune Response Against Meningitis
Photo taken in Ban Nong Rang Ka, Thailand

In a first of its kind study, the commensal bacteria Neisseria lactamica (Nlac), when engineered to express a protein derived from the pathogenic bacterium Neisseria meningitidis (Nmen), elicited immune responses—characterized by both antibody and memory B cell responses—against the Nmen protein when introduced into the noses of healthy volunteers via nose drops.

The results are published in the journal Science Translational Medicine.

Meningitis occurs in people of all age groups but affects mainly infants, young children, and the elderly. Meningococcal meningitis, the bacterial form of the disease, can lead to rapid death after symptoms start.

Nlac is a natural commensal of the nasopharynx. By occupying the nose, it helps protect from meningitis by denying a foothold to Nmen. A previous study showed that nose drops of Nlac prevented Nmen from settling in 60% of participants. Since then, researchers have aimed to make Nlac even more effective at displacing Nmen.

Because experimental, intranasal, infection of human adults with Nlac produced safe, sustained pharyngeal colonization, the bacterium has potential utility as a vehicle for the release of antigens to the immune system.

When Nlac was engineered to express a vaccine antigen, the system induced systemic, antigen-specific, immune responses in humans. More specifically, the authors wrote that, when Nlac expressing the meningococcal antigen Neisseria Adhesin A (NadA) was inoculated intranasally into human volunteers, all colonized participants carried the bacteria asymptomatically for at least 28 days, with most (86%) still carrying the bacteria at 90 days.

The controlled infection was safe, and there was no transmission to adult bedroom sharers during a three month period.

Jay Laver, PhD, senior research fellow in molecular microbiology at the University of Southampton, U.K., commented: “Although this study has identified the potential of our recombinant N. lactamica technology for protecting people against meningococcal disease, the underlying platform technology has broader applications.” It is theoretically possible, he added, to express any antigen in our bacteria, which means we can potentially adapt them to combat a multitude of infections that enter the body through the upper respiratory tract. In addition to the delivery of vaccine antigens, he noted, “advances in synthetic biology mean we might also use genetically modified bacteria to manufacture and deliver therapeutics molecules in the near future.”