Vaccines could offer hope - but who to vaccinate, and against what, has no clear answer yet.
By Pierre Meulien, Director, IMI
As bacteria get better at mounting defences against antibiotics, standard treatments no longer work for some common infections. Scientists are still identifying new ways to kill dangerous microbes, but over the long term, this will not be enough. Bacteria will inevitably acquire resistance to whatever new antibiotics we throw at them, and the problem will remain. What’s more, we know now that any new antibiotics will have to be used sparingly, and this presents a problem that is only indirectly related to science: how do you convince a drug manufacturer to develop something that should be used only in exceptional circumstances? The business case is glaringly weak.
Target, bug and setting: designing clinical trials for vaccines
There are few things we can do. Vaccines are a particularly promising avenue of research because they are resistance-proof. The vaccine induces an immune response and the bug is neutralised, meaning it doesn’t get a chance to mutate – there is no infection, and thus no need for an antibiotic. It’s certainly not a novel idea; there are already a number of vaccines against different bacterial diseases, like whooping cough, diphtheria, tetanus and otitis media. But designing clinical trials for new vaccines against bacteria-induced infections poses problems that have yet to be solved.
The question is: what bacteria-induced conditions do we vaccinate against? And in which target population? Perhaps epidemiology could help answer the first question; is there a resistant strain of E. coli circulating? Then perhaps we vaccinate against that. The question of who gets vaccinated has no clear answer. This makes it difficult to design clinical trials, and it’s one of the reasons the field has been relatively quiet. If we can get clever about defining the target, bug and setting, we could be on track to avert disaster
From basic science to market rewards
A public private partnership like IMI is the right vehicle for making progress on these R&D challenges. IMI has invested heavily in AMR. The research is wide-ranging, from the study of the permeability of Gram-negative bacterial cells, a fundamental problem in antimicrobial research (TRANSLOCATION), to the promising trials in the use of monoclonal antibodies to prevent staphylococcus infections in hospitals (COMBACTE-NET). VALUE-DX is looking at the culture around prescribing antibiotics; how could encouraging the use of rapid diagnostics and cut down on unnecessary prescriptions, while DRIVE-AB modelled different market rewards and drew up recommendations for policy makers on how to incentivise new antibiotic development.
These projects have resulted in a highly networked community; the right people who can move the field on a number of extremely tricky questions have been brought to the table thanks to IMI. The network created by the projects like COMBACTE-NET has attracted attention from AMR initiatives around the world, allowing the global public health community to pool the best scientific minds to tackle one of the most daunting challenges of our time. Some of the conversations may be difficult but they are necessary. And a public-private partnership seems to be the best place for these high-stakes conversations to take place.