New research has found that rates of disease caused by a common bacterium could be substantially reduced by changing our approach to vaccination.
Researchers from the Wellcome Sanger Institute, Simon Fraser University in Canada and Imperial College London combined genomic data, models of bacterial evolution and predictive modelling to identify how vaccines could be optimised for specific age groups, geographic regions and communities of bacteria.
These ideas will be critical for applying lessons learned from introducing vaccines in high-income countries to combatting the disease where the burden is highest. Dr Nicholas Croucher
The team estimate that tailoring vaccines to the strains of bacteria circulating in a particular region, or redesigning vaccines for different age groups, could significantly reduce invasive disease.
The study, published today in Nature Microbiology, simulated the performance of vaccines over time to assess the risk of vaccine-targeted strains of the bacteria being replaced by other potentially dangerous strains. Through this predictive modelling approach, the researchers identified new vaccine designs that could help reduce overall rates of disease.
S. pneumoniae can cause serious bacterial infections such as pneumonia, sepsis and meningitis – known collectively as invasive pneumococcal disease (IPD).
Approximating vaccine effectiveness
Vaccines against S. pneumoniae have prevented millions of infections, but are not always effective because infection can be caused by different serotypes – groups of strains with similar features. Each part of a vaccine usually protects against a single serotype, with the most complex vaccine (PCV13) targeting 13 serotypes.
Because there are approximately 100 S. pneumoniae serotypes around the world, vaccine effectiveness varies between countries depending on which serotypes are present in the population. When serotypes are removed from circulation by a particular vaccine, other serotypes of S. pneumoniae rise to take their place. Some of the new serotypes, however, can be more dangerous than the original ones.
In this study, the researchers optimised a computer model to approximate the effect of vaccines targeting different serotype combinations. Analysis of vaccine effectiveness was then carried out on S. pneumoniae genomic data from Massachusetts, USA and the Maela refugee camp in Thailand.
The complexity of S. pneumoniae vaccines means many designs are possible, each with different effects on disease. In Maela, for example, the presence of 64 S. pneumoniae serotypes means around 100 trillion vaccine designs are possible.
But it would take 19,000 years to simulate them all, with most being sub-optimal. The researchers developed a more efficient method that made it feasible to identify the best-performing designs from the trillions of possibilities.
The team discovered that rates of infant IPD in Maela could actually be reduced by omitting components from the PCV13 vaccine to allow certain serotypes to remain in the population, removing the possibility of their replacement by highly invasive serotypes. In Massachusetts, a vaccine targeting 20 serotypes was found to be more effective than the current PCV13.
Accelerating future vaccine discovery and design
The results highlight the need for vaccine programmes to be tailored to specific communities of bacteria.
Dr Nicholas Croucher, of the MRC Centre for Global Infectious Disease Analysis, Imperial College London, said: “Our research shows that the best vaccine designs strongly depend on the bacterial strains present in the population, which vary considerably between countries.
“The best vaccine designs also depend on the age group being vaccinated. These ideas will be critical for applying lessons learned from introducing vaccines in high-income countries to combatting the disease where the burden is highest.”
The approach we describe in this study will play an important role in accelerating future vaccine discovery and design to help reduce rates of disease. Professor Jukka Corander
Vaccination of infants also affects IPD in adults. However, trends in IPD can differ between infants and the elderly in the same country, as seen recently in the UK. In many places, older adults already receive an S. pneumoniae vaccine, which was designed before the infant vaccine. The study also found that adult disease rates could be reduced by almost 50 per cent by redesigning adult vaccines to complement those administered to infants.
Professor Caroline Colijn, of Simon Fraser University and the Wellcome Sanger Institute, and a Visiting Professor in the Department of Mathematics at Imperial, said: “This approach to optimising vaccines will help to address several problems, such as invasive disease among infants or adults and minimising antibiotic resistance in the post-vaccine population.
"Such an approach also enables public health policymakers to assess the likely effectiveness of an existing vaccine for a local population based on genomic surveillance data.”
Professor Jukka Corander, of the University of Oslo, University of Helsinki and the Wellcome Sanger Institute, said: “With the power of the latest DNA sequencing technology we are heading towards a future where large-scale genomic surveillance of major bacterial pathogens is feasible. The approach we describe in this study will play an important role in accelerating future vaccine discovery and design to help reduce rates of disease.”
This research was supported by the Engineering and Physical Sciences Research Council of the UK, the Government of Canada’s Canada 150 Research Chair program, Wellcome, the Royal Society, the UK Medical Research Council and the European Research Council.
‘Designing ecologically optimised pneumococcal vaccines using population genomics’ by Caroline Colijn, Jukka Corander and Nicholas J. Croucher is published in Nature Microbiology.
Top image credit: SELF Magazine
Based on a press release by the Wellcome Sanger Institute.
Article text (excluding photos or graphics) © Imperial College London.
Photos and graphics subject to third party copyright used with permission or © Imperial College London.
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