Dark times

We’ve been hunkered down over the dark winter months in Edinburgh planning experiments and looking at data, and now that we are in a spell of warm spring weather we realise we’ve completed not one malaria challenge but two. Almost all of our participants in the BIO-004 trial returned for re-challenge in February (it went swimmingly) and we are now starting to plan for the third and final challenge, which kicks off in around 6 weeks. This will be the most complex step in the trial as we challenge half of the participants with falciparum malaria (which is widespread in sub-Saharan Africa) and the other half with vivax malaria (most commonly found in Asia and South America). Malaria is a truly global disease and the world is quickly changing around us - the decisions that have been taken by just a few will have a profound impact on malaria control for hundreds of millions who don’t have a voice in the debate. A recent report in the British Medical Journal makes plain the challenges we now face: https://www.bmj.com/content/389/bmj.r783.

In the thick of it

We’re 9 days into our first malaria challenge in the BIO-004 trial. We’ve been up early to ready the clinic for challenge, up late measuring parasites and gift-wrapping heavy water, and working around the clock to ensure participant safety. Samples are being carefully banked for all of the science we’ve got planned and we’re already looking at data.

It’s hard to overstate the sheer number of people involved in a malaria challenge study (we’ll set this Q with a prize for the closest answer in our Discord at Christmas) or the incredible commitment from our participants. And we’re expecting things to get really busy next week when we start the intensive sample collection after we treat the participants with anti-malarials. This is when we can really examine the immune response to see what’s up. Wish us luck! And we’ll see you on the other side once the first challenge is complete.

Question Time

Do you want to know what happens on a malaria challenge day? Or how much force is required to take a bone marrow sample? Or maybe you wonder what we can learn about children in Africa by studying adults in the UK? Last night we ran a live event where we talked about the science behind the BIO-004 clinical trial and then opened the floor for any questions from our audience. They really put us on the spot! And you can watch the whole thing right here. Find out why we need to change the way we protect children against malaria and how we keep our volunteers safe when they take part in a malaria challenge study.

We're underway!

Sorry for having been a little quiet - it’s only because our BIO-004 clinical trial has finally started! Five years in the making, we couldn’t be more excited that our first 11 participants have received their yellow fever vaccination! Of course, we have their well-being at heart and supply them with a well-stocked snack box at all times. :) The Spence lab team has set-up camp in Oxford, processing blood like ninjas, and the first trial samples have already arrived back in Edinburgh. What a ride! We are still recruiting for our second group of 11 - so if you know someone who might be interested check out https://trials.ovg.ox.ac.uk/trials/bio-004.

Remarkably, while all of this was going on, Katharina, Matteo, and Jo still managed to go to the pub... well to Skeptics in the Pub. Watch them explain why we infect people with malaria to understand how the immune systems learns to tolerate malaria parasites.

World Malaria Day

It’s easy to be so focused on your research that you lose sight of the impact malaria has on individuals and families. However, today is an important moment to step back and take it all in. We made enormous progress in reducing malaria deaths by almost 50% between 2000 and 2015, but progress has stalled in the last 10 years. Today, we are still witnessing almost 600,000 deaths a year, mainly among children under 5 years of age. Each one of these is a tragedy.

There is some cause for optimism, with vaccines soon to be introduced at scale. These can work alongside bed nets, insecticides, and drugs to bring down rates of infection. But our optimism needs to meet realism. Today we are making important but incremental steps, and there will continue to be hundreds of thousands of deaths from malaria.

At the MAM Conference in February, we heard from the Bill and Melinda Gates Foundation, who are aiming to reduce infection rates by 80-90% in the first 3-5 years of life. This would be an incredible achievement, but even in this best-case scenario, what would happen to these children when they stop receiving the vaccines and drugs that protect them?

It’s easy to forget all of the good work that has come before your own endeavour, but history would tell us that exposure to malaria at 6 or 10 or 12 years of age does not have a happier ending. That is why we need to understand how to stop infection from causing disease. We’ll be talking about this at a virtual event next week and everyone is invited to join in the conversation.

We shouldn’t wait to see what happens when infection rates fall. We already know.

How we got here

If you want to know more about the background to the BIO-004 trial, you can check out our earlier work on the VAC063 and VAC069 studies. These clinical trials tested candidate malaria vaccines in volunteers who underwent controlled human malaria infection. On the side, we were able to use samples from these trials to study damaging immune responses to malaria and to learn which parts of the immune response had to be switched off to promote health.

This was all made easier because we were able to compare the immune response to Plasmodium falciparum (the most deadly malaria parasite) with Plasmodium vivax (which causes high fever but not severe disease). You can watch Phil explain these trials, their results and what it all means during his Keynote Lecture at the EMBL Malaria Conference (BioMalPar).

And just last month, Wiebke was presenting our very latest data on controlled human malaria infection at the MAM Conference in Australia. We’ll get you up to speed with what we said, what we heard and what we saw next month. If you’re keen to get a sneak-peak, check out our Instagram : )

Start your engines

We are in full swing recruiting participants for the BIO-004 clinical trial, which will tell us how people learn to switch off damaging immune responses to malaria parasites. We think this can tell us how children become immune to severe forms of malaria after only a handful of infections and without being able to effectively kill parasites. This could be game-changing for malaria immunology and disease control, and we couldn’t be more excited to get started after 5 years of planning.

We expect the trial to kick off in June 2024 and run for about 20 months. this will give us all of the samples we need to answer our questions (and keep us busy to retirement). To get everyone up to speed we’ve posted a video that explains the BIO-004 trial and the science behind this study. If you come back each month you’ll hear all of our trial and research-related news, as well as updates on our other big lab projects.

And if you have any questions or want to talk science, join us on our Discord. It’s a friendly place.