In 2013 a new vaccine to protect against meningococcal group B disease (Men B) was licensed for use in Europe. Bexsero is a new type of meningitis-preventing vaccine as it triggers an immune response based on four proteins expressed in the bacteria, rather than its ‘sugar coat’ – the polysaccharide capsule. 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 Men B bacteria, or it could be detrimental, reducing the carriage of related harmless strains of the same family (Neisseria) that could protect against disease.
This research, which began in May 2015 at Imperial College London, will 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 (meningococci) has relied on growing bacteria found on swabs from the back of people's throats, an approach which has great limitations through the many assumptions that have to be made about what organisms might be there, to allow suitable growth conditions to be used. This research will instead use state of the art technology which can identify bacteria found in throat swabs from their DNA signatures, with no need to grow them at all.
Using this approach, Professor Simon Kroll and Professor Paul Langford will:
- analyse samples which have been collected periodically from the throats of 200 babies over the course of their first three years of life
- analyse samples from the throats of 160 under-threes who have participated in Bexsero phase II clinical trials
This will allow 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 pathogenic meningococci that are present. They will be able to describe the normal pattern of bacterial carriage in healthy babies, and discover the impact of Bexsero on carriage of both meningococci and related harmless bacteria. Their results should inform other studies, of whether previous carriage of these bacteria has any impact on vaccine effectiveness.
The development and introduction of a vaccine which protects against many strains of Men B is a huge breakthrough in the fight against this disease. However, as Bexsero does not protect against all strains of Men B, there is still significant work to do before the disease is fully preventable. As more vaccines are developed and refined, it is important their wider impact is understood. This helps policy makers ensure our vaccine strategies are as effective as possible.
By assessing the effects on bacterial carriage following vaccination with Bexsero, this work will play a vital part in this process. Ultimately, it will improve our understanding of the best, and safest, way to protect against Men B.
There will also be impact on improving understanding of acquired immunity to Neisseria in the most vulnerable years to meningococcal infection. Learning from this research may also play a role in helping inform future immunisation strategies, moving us closer to truly effective prevention and control of Men B.
This is a 30 month project which started in July 2015.
July 2016. In their first year, the team has collected clinical data and throat swab samples from a large group of healthy babies, and from a second group of infants who had participated in the Bexsero (Men B vaccine) clinical trial. They have extracted the bacterial DNA from these samples.
The team has given an oral presentation on their work at the European Society for Paediatric Infectious Diseases Research Masterclass in Brighton in May 2016.
September 2017. In the second year, the focus has been on the analysis of throat samples to address the questions of whether Bexsero vaccination alters the composition of the bacterial population in the throat.
Following the resolution of some technical problems with DNA sequencing, the team now has good quality data.
Amalgamated data highlights the changes in the bacterial population at the back of the throat as a child gets older, and shows a clear rise in the prevalence of Neisseria species as a child reaches 12 months of age. While the team has found the expected diversity of bacteria in the sample, and the levels of the two Neisseria species, they have not been able to detect an effect of immunisation on the carriage of either.
The importance of this result, if confirmed, is in providing a first answer to the question of whether vaccination reduces carriage of meningococcus. From results so far, this does not appear likely to be the case.
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This research is only made possible by the generous support of people like YOU. Help us continue by donating, or raising funds for our work. On behalf of everyone who will benefit, now and in the future.
Professors Paul Langford and Simon Kroll
Imperial College London
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