Developing new methods to assess immunity to pneumococcus after vaccination
Dr Helen Baxendale, Institute of Child Health, London
Dr Baxendale and her team developed new techniques to measure how effective existing meningitis vaccines are, as well as how effective new vaccines might be.
Encapsulated bacteria are major causes of meningitis in childhood in the UK. Pneumococcus and meningococcus type B are now the most common meningitis causing bacteria. There are many different types of pneumococcus that cause disease, and a polysaccharide vaccine that provides some protection in adults and older children has been available for over twenty years. More recently, a pneumococcal conjugate vaccine (Prevanar) has been developed that can protect babies and young children from pneumococcal infection.
Although Prevenar reduces pneumococcal disease in young children, it is not known how long this protection lasts. In addition, there may be some children who, despite seemingly good immunisation responses to conjugate vaccines, are not protected from severe infection -including meningitis – by this current vaccine strategy.
Dr Baxendale's team looked specifically at the new pneumococcal vaccine and at the immunity it induces. Since this study a new vaccine ‘Prevenar13’ has been introduced as part of the UK immunisation schedule.
By developing new laboratory techniques, Dr Baxendale and her team aimed to measure how a person's immune system responds over time to pneumococcal bacteria following immunisation, by refining the technology used to analyse blood samples from children and adults. This will enable them to measure the duration of effective immunity and to understand why, in rare cases, immunisation may fail to protect someone from pneumococcal disease.
This approach may then be applied to identifying potential new vaccine targets to improve pneumococcal vaccine coverage.
The information gathered through this project will enable better, longer lasting vaccines to be developed.
This project is now complete - see the outcomes tab for more information.
The researchers were able to develop a robust and reliable new laboratory technique to study the immune response against pneumococcal infection and vaccination using very small blood samples that would be acceptable to take from children.
Baxendale: “We set out to bring these assays to the stage that they can be used in a clinical setting for paediatric patients. In this context we have achieved what we set out to achieve.”
The technique is now being used in clinical studies to assess new vaccine candidates, to determine the duration of immunity after vaccination (which will inform future decisions on the national immunisation schedule) and to study cases of vaccine failure.
In addition to developing the assay, this study found a special type of immune cell, which produces a specific type of antibody that is potentially able to recognise various different serotypes of pneumococcus. Future vaccines able to stimulate the development of this type of cell may be effective against a wide range of pneumococcal serotypes.
Developing new techniques to assess the nature and duration of protective immunity to pneumococcus after vaccination
Dr Helen Baxendale, Institute of Child Health, London
Dr Baxendale and her team developed new techniques to measure how effective existing meningitis vaccines are, as well as how effective new vaccines might be.
A pneumococcal conjugate vaccine (Prevanar) licensed for use in the UK has been introduced into the infant immunisation schedule. Studies from the USA have demonstrated that Prevanar reduces invasive disease and colonisation in the first few years after immunisation for vaccine serotypes. However, the duration of the protection following immunisation with this and other conjugate vaccines is unknown.
Hib and Meningococcal C conjugate vaccine studies demonstrate that immunisation in early infancy results in high short term protection but has reduced long term efficacy relative to children immunised at an older age. This is despite evidence that both vaccines induce immunological memory in infancy, as defined by serological anamnestic responses and increasing antibody avidity with time post immunisation.
The team aimed to develop in vitro techniques to expand antigen specific memory B cells from small blood volumes to analyse the quality of follicular and marginal zone derived B cell memory with time post immunisation, and correlate this with serological responses. This allowed the team to analyse, at a level of detail not previously possible, molecular events following vaccination. This information could contribute to the rational design of vaccination schedules optimising the length of protection induced, irrespective of age at vaccination. The techniques may then be used to investigate cases of vaccine failure, identify alternative vaccine antigens and provide the foundation for future studies analysing the effects of carriage in maintaining the pneumococcus specific B cell memory pool.
This project is now complete - see the outcomes tab for more information.
A robust new assays system to track and quantify pneumococcal memory responses to pneumococcal antigens following immunisation has been established and is now being applied in clinical trials in adults and clinical studies in high risk paediatric patient populations.
These assays systems quantify the presence of circulating pneumococcal specific memory populations and evaluate how effective pneumococcal immunisation with different vaccines/vaccination schedules primes for lasting memory responses.
In paediatric studies, the techniques generated may be used to evaluate the quality of pneumococcal immunity following immunisation with existing pneumococcal vaccines. The data generated during these studies can be used to help optimise immunisation strategy in both healthy children and children with immunodeficiency- who are at increased risk of pneumococcal disease.
The assays developed in this study may also have a role in understanding vaccine failure – i.e. children who get pneumococcal meningitis despite immunisation.
One further element of the study was to investigate the potential role of natural antibody in protection from pneumococcal infection. The researchers were able to demonstrate that pneumococcal memory cells of IgM isotype dominate in the circulation of pneumococcal experienced adults. It was shown that this antibody is not serotype restricted, suggesting that it is likely to be effective against multiple pneumococcal serotypes.
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