Human immune response to experimental colonisation with Neisseria lactamica
Professor Robert Read, University of SheffieldÂ
The objective of this study was to look at how harmless bacteria, which live in the noses and throats of babies and young children, might help the immune system to develop antibodies to protect against Meningitis B.
At any one time, the majority of the population is naturally immune to the meningitis-causing bacteria Neisseria meningitidis, with one in ten of us having it living harmlessly in our noses and throats. This natural immunity is thought to be due to a harmless relative of Neisseria meningitidis, Neisseria lactamica, which also colonise people's noses and throats. This bacterium is efficient at colonising babies and infants, but is not detected frequently amongst teenagers and adults, apart from nursing mothers.
Previous studies suggest that a high prevalence of Neisseria lactamica is associated with a low incidence of meningococcal disease. Therefore, colonisation with Neisseria lactamica may be beneficial, and analysis of the immune response against this commensal may give clues about what a protective immune response against Neisseria meningitidis should look like. This would provide researchers with a ‘gold standard’ to assess responses to meningitis B vaccine candidates.
Professor Read's team introduced Neisseria lactamica into the noses of healthy adults and then measured their immune response to see if they made antibodies against the organism. They then determined whether these antibodies were also able to protect them against Neisseria meningitidis. Whilst live Neisseria lactamica bacteria are unlikely to be used as a vaccine in the general population, the project aimed to provide information concerning the scale and quality of the immune response to Neisseria lactamica, and provide a ‘gold standard’ with which to compare other responses generated by mucosal vaccines.
Although Professor Read anticipates that Neisseria lactamica is unlikely to be a vaccine candidate on its own, he is confident that what they learn about how the bacteria stimulates the body's immune response will be invaluable in the search for a successful vaccine.
This project is now complete - see the outcomes tab for more information.
The researchers discovered that Neisseria lactamica colonisation can prevent subsequent colonisation by Neisseria meningitidis, because all of the volunteers they had given Neisseria lactamica to did not catch Neisseria meningitidis, whereas some of the volunteers who had not been colonised by Neisseria lactamica did get infected with Neisseria meningitidis. This is excellent news, because it means that it may be possible to prevent Neisseria meningitidis from colonising the nose and throat and therefore from causing any disease, simply through colonisation with the harmless bacterium Neisseria lactamica.
Surprisingly, the team also found that this effect is caused by Neisseria lactamica directly and not by the immune system. This is an important finding, which will have to be investigated further to determine the exact mechanisms behind this effect.
Human immune response to experimental colonisation with Neisseria lactamica at University of Sheffield
Professor Robert Read, University of SheffieldÂ
The objective of this study was to look at how harmless bacteria, which live in the noses and throats of babies and young children, might help the immune system to develop antibodies to protect against Meningitis B.
It is considered that recurrent colonisation by commensal Neisseria lactamica provides natural immunisation against invasive disease caused by Neisseria meningitidis in infants and children. Neisseria lactamica is a common coloniser of infants but rarely colonises older children and adults, which may be the basis of the relative susceptibility of teenagers and young adults to meningococcal disease. In this project, the team developed the methodology for experimental intranasal challenge of adults with live Neisseria lactamica, and then measured antibody responses to Neisseria lactamica and cross-reacting responses to a range of Neisseria meningitidis proteins. The project also tested the hypotheses that (a) adults can be colonised experimentally with Neisseria lactamica, and (b) colonisation by Neisseria lactamica induces immunity that cross-reacts with antigens of Neisseria meningitidis. It also aimed to provide valuable information to help in the development of effective vaccines.
The team developed experimental colonisation of adult volunteers with Neisseria lactamica to determine if carriage could be established in adults, and whether immune responses that are cross-reactive with the meningococcus were elicited. Thus, the aim was to demonstrate whether carriage of this commensal Neisseria species could induce cross-protective immunity against meningococcal disease, and provide some measure of the scale and duration of the response elicited by Neisseria colonisation.
This project is now complete - see the outcomes tab for more information.
This project described the human immune response to Neisseria lactamica and discovered that this organism has the potential to retard colonisation by Neisseria meningitidis, probably by direct, rather than indirect, immunological mechanisms. The team concluded that inoculating Neisseria lactamica would have a significant effect on meningococcal colonisation in humans.
The researchers found that carriers of Neisseria lactamica developed humoral immunity to this bacterium including some opsonophagocytic, but not bactericidal antibodies that could cross-react with Neisseria meningitidis. The lack of bactericidal antibodies is an important negative finding that suggests that protection from Neisseria meningitidis colonisation is mediated by direct effects from Neisseria lactamica colonisation rather than cross-reactive immune responses. This project has therefore shown that it may be possible to prevent colonisation by Neisseria meningitidis by means other than vaccination.
MeningitisUK · Registered Charity No.1076774