While genomics is a powerful tool for informing pneumococcal vaccine design, counterintuitively it may not always be beneficial to target a given serotype. There is the possibility that removing a serotype might enable a more invasive one to expand in the niche that becomes available. This is particularly a worry with serotypes that have different disease effects in children and adults. Rolling out a vaccine targeting serotypes found predominantly in children may lead to replacement by serotypes that, while safer in children, cause an increase in invasive disease in vulnerable adult populations. More attention is therefore being given to predicting the consequences of vaccines, with a view to designing them in a way that leads to a more benign post-vaccine population.
Dr Nick Croucher, together with Sanger PaM programme associate faculty members Professor Caroline Colijn, Simon Fraser University, Canada and Professor Jukka Corander, University of Oslo, Norway, integrated genome data from GPS into an ecological model optimised to search for vaccine formulations that considered invasive disease burden after vaccination. Their model suggested that simply targeting the most invasive serotypes may not necessarily result in the greatest reduction in serious disease. Rather, the right formulation for a vaccine was shown likely to depend on which serotypes are circulating in a given population. An optimal vaccination strategy might therefore require vaccines that are individually formulated for different populations and geographic settings.
Unfortunately, PCVs are expensive to develop, produce and roll out. According to Professor Klugman, economies of scale mean that a vaccine formulated for a country/region is likely to cost several-fold more than a single vaccine that is rolled out globally. Furthermore, incorporating additional serotypes that provide greater protection mainly in low- and middle-income countries into updated PCVs has seen little pushback from manufacturers and funders to date, and has not resulted in a significant reduction in vaccine efficacy. However, as noted by Colijn, “We have no idea what the cost is of not developing the appropriate vaccine for the appropriate population. There could be a risk of deploying vaccines that may not work very well, and which undermine trust in the product and vaccination in general, which could impact lots of other infectious diseases worldwide. The people or groups that bear the cost of developing vaccines are not the same as those that bear the cost of not developing them”.
For now it seems, further work is needed to apply genomics to longitudinal carriage surveys of the pneumococcus and to assess the implications of such models in the real world.
While not a goal at the offset, over the past decade the GPS has become a poster-child for applying genomic surveillance for bacterial pathogens at sufficient scale to have real-world public health impact. Looking forward over the next decade, assuming that costs continue to fall and pathogen agnostic sequencing approaches can be developed and applied at scale for clinical samples, efforts to control many other pathogens will benefit from the lessons learned through GPS. In settings without adequate microbiology and antimicrobial susceptibility testing, obtaining antibiotic and vaccine susceptibility data directly from genome sequencing will become standard for tailoring treatment of individual patients. Interrogating genomic data through modelling will also enable a better understanding of pathogen evolution, selection, and responses to antimicrobials, vaccines or non-pharmaceutical interventions, strengthening public health policy overall.