Neisseria in the oropharyngeal microbiome - relationship to MenB vaccination explored by non-culture methods.
In 2013 a new vaccine (Bexsero) to protect against disease caused by Neisseria meningitidis (meningococcus) serogroup B, (MenB) was licensed for use in Europe; it was introduced into the UK routine immunisation schedule in September 2015. Bexsero is a new type of meningitis-preventing vaccine that triggers an immune response based on four proteins expressed in the bacteria, rather than the polysaccharide capsule (sugar coat). One important unanswered question is whether this vaccine will reduce carriage of bacteria in the nose and throat. If it does, this could be of overall benefit by reducing carriage of harmful MenB bacteria; but there is the possibility that it might be detrimental, reducing the carriage of related harmless strains of the same family, for example Neisseria lactamica or Neisseria cinerea, that have been speculated to generate protective immunity to MenB disease in the course of carriage.
What the research team planned to do
This research, which began in July 2015 at Imperial College London, aimed to provide crucial insights into how bacteria colonise young children’s throats during their first three years of life and how this is impacted by Bexsero.
Previous research into the carriage of meningococcal bacteria has relied on growing bacteria found on swabs from the back of people's throats; this culture-based approach has great limitations because of the many assumptions that have to be made about what organisms might be there, and hence the most suitable growth conditions to use. This research used state of the art technology to identify the DNA signatures of bacteria found in throat swabs, with no need to grow them at all.
Using this approach, Professor Simon Kroll and Professor Paul Langford:
- analysed samples which had been collected periodically from the throats of 200 children over the course of their first three years of life
- analysed samples from the throats of a further 179 children under three years who had participated in Bexsero phase II clinical trials
This allowed them to describe the whole bacterial population living in the back of the throat and define in detail the strains of both harmless bacteria and potentially harmful meningococci that were present. They were able to describe the normal pattern of bacterial carriage in healthy babies and investigate the impact of Bexsero on carriage of both meningococci and related harmless bacteria.
Summary and impact of results
This project has developed a new approach to studying the carriage of Neisseria – a non-culture approach based on extracting DNA from throat swabs and using next-generation genetic sequencing to reveal the composition of the colonising population in great detail. The researchers analysed serial throat swab samples from 200 healthy children, collected repeatedly over three years, to establish the normal progression of bacterial colonisation during early life. They identified the harmless, and potentially protective, Neisseria species – Neisseria subflava, cinerea and lactamica – which predominate during that period. In samples collected from the second group of 179 infants who were participants in a trial of the meningococcal vaccine Bexsero® (now given to all babies in the UK), the researchers were able to show that reassuringly, vaccination does not have a perceptible, deleterious effect on the carriage of these three, or other harmless, species of Neisseria.
Carriage of potentially invasive, and so harmful, meningococci is very rare in early life, so the impact of Bexsero vaccination on meningococcal carriage could not be assessed in the two groups of young children. However, this new approach should be ideally suited to studying the impact on carriage of Neisseria in late adolescence when as many as 30% of individuals may carry meningococci; and help to define any place the vaccine may have in the protection of these older individuals.
This new approach to studying bacterial carriage is far more informative than existing, culture-based methods and should make a significant difference to clinical epidemiological studies; not just for Neisseria species, but also for other bacteria that cause meningitis and septicaemia.
This approach will also aid studies on the impact of vaccination on bacterial carriage in older individuals and hence assist in the development of vaccine policy that provides protection to as many people as possible; through both direct and indirect effects.