Nose drops with “friendly” bacteria show promise to protect against meningococcal meningitis
In a first-of-its-kind study, researchers slipped a genetically modified gene into harmless carrier bacteria and then inserted the “package” into each study participant’s nose via nose drops. The result was a strong, long-lasting immune response against the very bacteria that can cause life-threatening meningococcal meningitis.
This opens the door to a new, long-lasting vaccine approach for bacterial meningitis as well as other infections sharing similar mechanisms.
The study was led by Professor Robert Read and Dr. Jay Laver from the NIHR Southampton Biomedical Research Centre and the University of Southampton, both located in Southampton, England.
Prof Read, Director of the NIHR Southampton Biomedical Research Centre, said, “This work has shown that it is possible to protect people from severe diseases by using nose drops containing genetically modified friendly bacteria. We think this is likely to be a very successful and popular way of protecting people against a range of diseases in the future.”
Root of the Problem
Neisseria meningitidis (meningococcus) is the leading cause of bacterial meningitis, a potentially life-threatening infection of the thin lining that surrounds the brain and spinal cord. The disease can cause severe brain damage and is fatal in 50% of cases if left untreated. Meningococci can also trigger sepsis, which infects the bloodstream . 1, 2, 3
This fastidious, encapsulated, aerobic gram-negative diplococcus is further credited with causing pneumonia and occasionally focal infections, such as arthritis, myocarditis, pericarditis, endophthalmitis, epiglottitis, otitis, and urethritis. It’s a cast of illnesses that all live under the unwelcome umbrella called meningococcal disease.
Meningococcal meningitis is of particular importance because of its potential to trigger large epidemics as well as isolated fatal outcomes when left untreated. Specific to bacterial meningitis, the disease strikes anyone at any age, although a disproportionate number of patients are children younger than 1 year old and those 16 through 23 years old.4
It’s estimated that 1 in 10 people have the Neisseria meningitidis bacteria living in the back of their nose and throat. Sometimes the bacteria quietly take up residence with no signs of disease. However, these folks are carriers, and they can transmit the bacteria to others—who might develop a meningococcal disease .5
Meningococcal disease cases in the United States have declined since the late 1990s—in part due the development of vaccines that help protect against certain types of bacterial meningitis. The most recent statistics, recorded by the Centers for Disease Control and Protection, state that in 2019 there were about 371 cases of meningococcal disease reported in the United States.5
As Nature Intended
Neisseria lactamica (N. lactamica), another bacterium, also naturally lives in some people’s noses. When things work well, Neisseria lactamica blocks the sinister Neisseria meningitidis from developing into meningitis disease.
In the afore mentioned trial, titled A recombinant commensal bacteria elicits heterologous antigen-specific immune responses during pharyngeal carriage, the research team built on their previous work that focused on this natural bacteria-driven impediment. 6
In their previous study, the researchers showed that in 60% of study participants the nose drops pumped up with N. lactamica elicited immune responses—characterized by both antibody and memory B cell responses—against the Neisseria meningitidis protein.
These results led the team to strengthen this safety net against meningitis disease by giving N. lactamica a “sticky” surface that could hold it for even longer to the nose lining. This was accomplished by replicating the very same sticky surface protein that allows N. meningitidis to grip onto cells lining the nose. The scientists copied and inserted the gene that codes for this protein into the DNA of N. lactamica, giving it better stickiness and a stronger ability to fend off meningitis.
The results of this unique study came as welcome news. The modified N. lactamica stayed in the nose longer, for at least 28 days, and 86% of participants still carried it at 90 days without any adverse symptoms.
According to a press release for the study, these results are “promising” as a new way to prevent life-threatening infections without drugs. “It’s an approach that could be critical in the face of growing antimicrobial resistance,” the press release added.
Dr Jay Laver, Senior Research Fellow in Molecular Microbiology at the University of Southampton, said, “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 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, advances in synthetic biology mean we might also use genetically modified bacteria to manufacture and deliver therapeutics molecules in the near future.”
1. World Health Organization. Meningococcal meningitis. Available from https://www.who.int/news-room/fact-sheets/detail/meningococcal-meningitis
2. Centers for Disease Control and Prevention. Meningococcal Disease. Available from https://www.cdc.gov/meningococcal/index.html
3. Centers for Disease Control and Prevention. Meningococcal Disease. Causes and Spread to Others. Available from https://www.cdc.gov/meningococcal/about/causes-transmission.html
4. Centers for Disease Control and Prevention. Meningococcal Disease. Age as a Risk Factors. Available from https://www.cdc.gov/meningococcal/about/risk-age.html
5. Centers for Disease Control and Prevention. Meningococcal Disease. Causes and Spread to Others. Available from https://www.cdc.gov/meningococcal/about/causes-transmission.html
6. Laver JR, Gbesemete D, Dale AP, Pounce ZC, Webb CN, Roche EF, Guy JM, Berreen G, Belogiannis K, Hill AR, Ibrahim MM, Ahmed M, Cleary DW, Pandey AK, Humphries HE, Allen L, de Graaf H, Maiden MC, Faust SN, Gorringe AR, Read RC. A recombinant commensal bacteria elicits heterologous antigen-specific immune responses during pharyngeal carriage. Sci Transl Med. 2021 Jul 7;13(601):eabe8573. doi: 10.1126/scitranslmed.abe8573. PMID: 34233953.