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Case study: Efficient and effective vaccination against pneumococcal disease

The success of pneumococcal vaccination

As an associate professor in paediatrics and vaccinology, Professor Matthew Snape knows just how useful vaccines are. When a new vaccine is introduced, it is reasonable to expect to see an impact on the disease targeted, and the pneumococcal vaccine first introduced in 2006 was no exception.  

Streptococcus pneumoniae are bacteria that are frequently found in the upper respiratory tract of healthy children. These bacteria cause a range of infections, from mild ear infections to pneumonia, meningitis, and sepsis, which can be fatal. Pneumococcal infections claim the lives of over 500,000 children per year. Children under two years old and the elderly are at highest risk.  

The pneumococcal vaccine has been a huge success story in the UK and around the world. It was quickly introduced to wealthy nations and thanks to GAVI, the Vaccine Alliance, also to low- and middle-income countries (LMICs). The charity has rolled out the vaccine to children in 60 countries to date, and it is expected to result in 700,000 prevented deaths by 2020 

Yet between 2015 and 2017, Professor Snape of the Oxford Vaccine Group, Department of Paediatrics at the University of Oxford led the NIHR-funded ‘Sched3’ study, which resulted in the Joint Committee for Vaccines and Immunisations (JCVI) recommending that the NHS give a reduced dose schedule for the infant pneumococcal vaccine programme. The study, supported by the NIHR Oxford Biomedical Research Centre, also provided data that will inform the cost-effective use of this life saving vaccine in LMICs. 

Reducing the number of needles

In the UK and many other countries around the world, the pneumococcal vaccine is administered to infants three times: at two, four and 12 months of age. The first doses are known as priming doses and the follow-up as a booster.  

Professor Snape explains how it may now be possible to reduce the number of vaccines given to babies and children without increasing their risk of serious and fatal infections: “When the NHS introduced the pneumococcal conjugate vaccine, we provided direct protection against pneumococcus to children receiving the vaccine, and also reduced circulation of these bacteria through the whole population.  

“There are over 100 different types of pneumococcus, some good and some bad. The current vaccine includes 13 types of disease causing pneumococcus, so very few people are carrying these 13 types any more. Therefore we realised that it may be possible to reduce doses and reduce costs without reducing effectiveness.”  

Professor Snape and his team believed that having achieved significant reductions in bacteria circulation, giving a reduced schedule with a single priming dose at three months and a booster at 12 months could generate sufficient concentrations of pneumococcal-specific antibodies to maintain control of this disease. 

The Sched3 study was led by the Oxford Vaccine Group in collaboration with Public Health England, with funding by the NIHR Policy Research Programme and the Bill and Melinda Gates Foundation. It was run with the National Vaccine Evaluation Consortium (NVEC), led at the time by Professor Liz Miller, who was a co-lead on the study, along with Professor David Goldblatt at University College London. The NVEC approached the Oxford Vaccine Group to lead on this study, because of their experience at recruiting large numbers of children to vaccine studies. 

Between September 2015 and June 2016, over 200 infants were enrolled and randomly allocated to receive either the usual three doses of the pneumococcal vaccine or the proposed two dose regime, in order to determine whether a reduced dose schedule could generate sufficient concentrations of the right antibodies to maintain control of the disease. Infants were given blood tests at five and 13 months old, to compare antibody levels between the two different vaccine schedules. 


Policy changes around the world

Professor Snape explains: “The study was the first of its kind to look at antibody responses to a booster dose of the pneumococcal vaccine after just a single infant priming dose. We saw that responses to most of the 13 strains covered by the vaccine were similar or superior after the reduced dose. Our work laid the foundation for moving to a reduced vaccine schedule in countries where a mature vaccine programme is in place, coverage is high, and vaccine-type disease is well controlled.” 

He continues: “Our clinical trial of 213 children has directly informed policy for the UK immunisation strategy and is likely to have a global impact for one of the biggest killers of children around the world. Studies like ours are happening in India, Vietnam and South Africa. If they show similar results, GAVI funding for vaccine introduction in LMICs can go further.  We were very proud that the UK was the flagship for this.”  

The work has shown that if you have population control of pneumococcus, then it may be possible to step back and to continue to achieve the same effect with fewer doses of the vaccine. In the UK alone, this could potentially result in up to 800,000 fewer doses of infant pneumococcal vaccines per year, with reduced distress for the child and their parents and increased flexibility for the infant immunisation schedule.  

In January 2020, the Public Health England changed the infant vaccination schedule for pneumococcal vaccine from three doses to two. This could generate annual savings to the NHS of over £7 million in administrative costs, before the considerable cost of the vaccine itself is taken into account. 

Elsewhere, although the manufacturers provide the vaccine at lower costs in lower income countries, pneumococcal vaccines take up a large amount of GAVI’s budget. Some middle-income countries that cannot get support cannot afford to pay for it. Professor Snape concludes: “Our study and the UK immunisation policy show a potential route for introduction of this vaccine into even more countries. This evidence is guiding decisions about immunisation strategies that could help to save even more lives.” 

Images in the lab courtesy of Dr Sean Elias, Jenner Institute, University of Oxford.

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