See the world in a grain of sand

Use of the microparticle Nano-SiO2 as an adjuvant to boost vaccine immune responses in neonatal mice against influenza.

There is a paradox at the heart of vaccine development, the people need the vaccines the most are one in whom the vaccines work the least. This is particularly the case for the elderly, the immunocompromised (people whose immune systems are impaired for some reason) and the patient group my research focuses on, the very young.

Baby Steps

In our first 28 days of life (known as the neonatal period) we are particularly susceptible to infection. In part, this is because neonates have not previously been exposed to infections – the womb, for the most part is sterile, and so haven’t built up a protective immune memory. However, this is not the only difference in the neonatal immune system. When the body is first infected, there is an early wave of responses called the innate system. For reasons unknown (though I am applying for funding to solve this of this highly important question – funders take note) this early innate immune system in early life is less responsive than later in life. In particular, babies are not very good at spotting bacterial infections.

This lack of immune response enable infection of babies, bacteria can get a greater toehold prior to be being recognised. But additionally this has an impact on vaccine responses. Vaccines, as you may or may not know, work by tricking the body into thinking it has been infected, leading it you build up a protective memory that prevents subsequent infection with the real bug. This trickery is achieved by either smashing the bugs into little bits or by using weakened (attenuated versions). Those of you paying attention will know how we have been researching methods to weaken viruses and make better vaccines; if not now’s the time to catch up.

Super Sand

However, given babies struggle to detect full fat pathogens they do even worse with the lite, vaccine versions of bacteria. This is where our current research comes in. It is possible to pep up a vaccine by adding substances called adjuvants. Adjuvants are often made of bits of bacteria, which trigger the immune system through a family of receptors called the TLRs (Nobel Prize fans – which year and who won the Nobel for discovering this – bonus point for knowing which animal they were found in). But as you now know, babies don’t recognise bacteria and therefore bacterial and therefore bacterial derived adjuvants are ineffective in early life. We took a different tack. The immune system, doesn’t just recognise infection, it recognises damage to cells. This cellular damage is detected by something called the inflammasome. We therefore tried a number of compounds which have been described as inflammasome activators. We settled on three – NanoSiO2 (which is really, really tiny grains of sand), CPPD (Calcium pyrophosphate dehydrate which causes an arthritis like disease called pseudogout) and the M-Tri-Dap (or N-acetyl-muramyl-L-Ala-γ-D-Glu-meso- diaminopimelic acid, part of the bacterial wall). We combined the compounds with flu vaccines to test whether it would improve the response. Amazingly mixing flu with sand, significantly improved the response. But then again, maybe it wasn’t that surprising as everyone knows, sand gets everywhere, is irritating and leads to a strong reaction ‘No you may not have a sand pit’. You’ll find all the details here.

Science, it's good for EU

This project was funded by the EU, which is something to consider very carefully – if we Brexit no-one would fund us to put sand in vaccines and the world would be a worse place. Britain is a huge net beneficiary of EU science. Not only in monetary value, but also in access to the best minds, facilities and resources.