The small trial – the first of its kind – showed that all the participants were still carrying the bacteria asymptomatically in their nostrils for at least 28 days, with the majority (86 percent) still carrying it 90 days later. It also produced a strong immune response.
Even better, this quick and convenient way of providing protection against infection could be applied to block out other types of bacteria and disease – something that’s badly needed with increasing antimicrobial resistance to existing drugs.
“This work has shown that it is possible to protect people from severe diseases by using nose drops containing genetically modified friendly bacteria,” says Robert Read, a professor of infectious diseases at the University of Southampton in the UK.
“We think this is likely to be a very successful and popular way of protecting people against a range of diseases in the future.”
The Neisseria meningitidis bacterium targeted by these nose drops occurs naturally in the nose and throat of around 10 percent of adults; unfortunately, in some cases it can invade the bloodstream, leading to life-threatening conditions such as meningitis (hence its Latin name).
Here, the scientists used a genetically modified version of the benign N. lactamica, also a naturally occurring nasal bacterium. In a previous study, N. lactamica had been shown to prevent N. meningitidis from settling in around 60 percent of participants.
However, it wasn’t just a matter of making the friendly bacterium colonize the nose instead of its more dangerous cousin. The key here lies in the genetic modification of N. lactamica (helpfully labelled GM-Nlac by the researchers) – by carrying an added gene for the sticky surface protein that N. meningitidis uses to grip the cells inside the nose, the helpful bacteria would introduce it as an antigen to the person’s immune system.
Antigens are various substances that our immune systems can use to generate antibodies against the pathogens associated with them; a controlled introduction of antigens to generate an immune response is how most vaccines work, for example.
In the case of these bacteria-laden nose drops, the resulting immune response was stronger and longer-lasting compared with controls, making GM-Nlac a promising candidate for generating immune responses to meningitis bacteria.
“GM-Nlac can be deployed safely, survive in its biological niche, and be effectively eradicated as necessary without transmitting to other adults living in close proximity to the study participants,” write the researchers in their published paper.
If bacterial meningitis takes hold in the blood stream, it can result in serious complications as well as other problems like blood poisoning, as the tissue around the brain and spinal cord begins to swell up. Death can occur in as little as four hours after symptoms start.
Around 1,500 cases of this meningococcal meningitis are reported each year in the UK alone, but science is fighting back: previous research has looked at ways of using antipsychotics to protect against the disease.
The researchers think their newly described approach could be used to modify other bacteria to protect against other types of infection, though it’s still early days for the technique.
“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,” says molecular microbiologist Jay Laver, from the University of Southampton.
“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.”
The research has been published in Science Translational Medicine.