An audacious DARPA plan to arm your cells against Ebola

During an infection, the cellular ranks of our immune system army fall into two different squads: Rhinos and Elephants. While the Rhinos’ orders are to charge headlong at the invader (on the double!), the Elephants have a more subtle objective: remember this enemy.

If you win the battle against the maraudering microbe, the brave and knackered fighters of Rhino squad are rewarded with “early retirement”1, but the Elephants (actually called ‘Memory Cells’) live on and await a repeat encounter with the enemy. Should the bug come back, the memory cells rapidly turn Rhino and destroy the germ before it can so much as dig a trench.

When we vaccinate ourselves against an infection, what we’re trying to do is build up a squad of germ-specific memory cells without having to go through the pain of getting the disease the first time around. This is a miraculous medical tool – just look at the number of infections per year in the US before and after vaccines.

The problem with vaccines is that they are difficult2 and time-consuming to develop. When a brand new virus species causes an outbreak in the future, we will need another strategy to stop its spread in the short-term: vaccines are for old foes, not the new disease on the block.

But an interesting project underway at the Defense Advance Research Projects Agency (DARPA) is aiming to give us rapid vaccine-like powers by transferring the immunological memory from a single person to everybody else.

To understand how it works we have to return to the memory cell squad of our army. Just like a regular army, the memory cells comprise separate units which attack at short or long-range. It is the long-range attackers, called B-cells, that are the focus of the DARPA project.

B-cells wage war by releasing sticky chemicals that plaster themselves on to specific microbes. When smothered in these chemicals the germ is prevented from going about its business and is painted as a target for destruction. If the chemical, called an antibody, sticks strongly to the right spot on the germ: hasta la vista, buggy.

Each of our B-cells is stuck in their way. When they’re growing up, they rearrange their DNA to try to make antibodies that stick better to incoming germs, and only those that succeed get the job. As the successful will only ever make one version of an antibody, we can look at the cell’s DNA, find the antibody’s genetic code and make it in the lab – no B-cell required. And this is where the DARPA project comes in.

As described in a story published on the website, the idea is to recover B-cells from survivors of disease (for example, people recovering from Ebola) and learn the genetic code for the best antibodies targetting the infection.

So far, so good. But the next step? Inject DNA containing the antibody code into the blood of uninfected people, where it will be taken up by cells in their body, decoded and used to start pumping out the antibody. Should these people then catch the disease, the bug doesn’t just have to worry about the regiments of the immune system, it has to worry about the armed civilian populace.

This plan is audacious, and there are plenty of reasons to be skeptical about its success. Even if you get to the stage where your cells are happily pumping out the antibodies, viruses can throw up a number of problems:

  • they could mutate; changing shape so the antibody doesn’t bind any more
  • if they spread directly between cells rather than being released out into the open spaces of your body, antibodies won’t have a chance to bind them (HIV and herpesviruses, for example)
  • they may already have countermeasures against antibodies (again, herpesviruses)

But even if the plan didn’t work against everything, that doesn’t mean it won’t against any. And if it does work? That would be incredible.

Head over to Fusion for the full story, including much more on the technology of vaccination using DNA and the hurdles standing in the way of the technique’s progress.

Linked article: DARPA thinks it has a solution to Ebola (and all other infectious diseases) – Fusion – Published on: 18 Mar 2015

  1. i.e. they all get told to commit suicide – a pumped-up army with nothing to shoot at is potentially dangerous for those left standing (that’s you, by the way).
  2. I covered (one of) the problems with testing Ebola vaccines in this article, but note, unlike my prediction from the data at the time, Ebola unfortunately remains live and well in West Africa.

Links to go viral – 16th March 2015

A day late, but a link longer. Here’s this week’s lovely links:

A live look at the AIDS virus – Science Magazine

So cool. Being able to image where a virus is hiding inside an infected animal or person is a big sci-fi-esque deal. Current bioluminescence imaging techniques, where the glowy-glowy genes of fireflies are engineered into viruses, are an excellent tool for studying virus spread in small animal models of infection. But what if you’re an AIDS researcher relying on larger animal stand-ins to study human disease? In this work, the authors used a system called immunoPET to see where simian immunodeficiency virus (SIV – a simian contemporary of the human virus, HIV) collected and spread inside live macaques. The system works by injecting SIV-specific antibodies into the macaques, which then lock on to the virus particles and stick to them. Cunningly attached to these antibodies are radioactive molecules that can be detected using a PET scanner (PET stands for Positron Emission Tomography, and is a fascinating medical tool). Thus, via the interface of antibodies, virology and PET combine to visualise the location and amount of virus deep inside the body. The work revealed unknown reservoirs of virus infection in the upper respiratory tract and could potentially act as an avenue for studying infection in people, though I’d guess that was some way off. Click through to see some great images of the work and more discussion.

Countries Reeling From Ebola Are Facing A Big Measles Threat – Buzzfeed News

Simply put: the current Ebola-afflicted countries had gotten complacent about Measles vaccination, had realised this and aimed to roll out large-scale vaccination campaigns – and then Ebola hit and ruined everything. The successful vaccination coverage in these countries is now way below where it should be. It’s also important to note that the same is true of other diseases. Western Africa would usually have a full anti-malaria campaign in action, but Ebola has wrecked the pre-existing healthcare infrastructure.

As an aside, this isn’t the first interesting science article I’ve read from Buzzfeed recently. Who knew it wasn’t just about the cats, lists and lists of cats?

Ebola survivors offer clues to body’s virus defences – Nature News

A small study has shed some light on the immune response to Ebola infection. The immune responses of four people treated at Emory University Hospital were assessed to understand how the human body combats the virus. Interestingly, the patients had strong T-cell responses to the virus nucleoprotein, which wraps up the virus genome. As our current vaccine attempts are targetted at driving an antibody response to the virus surface glycoprotein, this new information could help us develop a superior treatment against the virus. The big caveat to note is that these infected individuals received novel anti-viral treatment that could have interfered with the normal development of the immune response, and (of course) the sample size here is just four people.

‘Disease is no longer a problem’ claims deadly bacteria – The Guardian

All this talk about stopping Ebola, but has nobody asked the virus what it thinks? No: it’s just another form of discrimination. Whilst this is 99% political parody rather than microbiology, I couldn’t resist – a great article where pox virus stands in for a pox on the UK political landscape. Perfect.

Links to go viral – 8th March 2015

This week, viruses take to the air (via creatures with wings) and a chat about herpesviruses:

Study: “Wild bumblebees vulnerable to variety of viruses” – UPI

Honeybees toil endlessly to make delicious delicious honey, but just like you and me, they have their off days when they don’t feel the buzz. Mites, microrganisms and viruses are enough to put pupa off their pollen, and a sick hive can suffer reduced honey production to full colony collapse. With our vested interest in their well-being, we’ve swotted up on what blights our bees, but whether the unwelcome critters in our managed hives reflect those that bug bumblebees in the wild is less understood. Things I learned from the linked article: 1) there’s some spillover of viruses from our own workers to wild bee populations, with transmission possibly occurring from sharing the same flowers, 2) bee viruses have excellent names – black queen cell virus, deformed wing virus, acute bee paralysis virus, slow bee paralysis virus and sacbrood virus.

Wild birds may spread flu virus – BBC News

If our bees are propagating viruses that later swarm into the wild, birds provide the opposite flight path when it comes to flu.

I think the headline “Wild birds may spread flu virus” is kind of like saying “water flows downhill”, but the article itself is a useful look into how the H5N8 and H7N7 bird flu viruses are travelling around Europe. For instance, ducks on a farm in Yorkshire in the UK may have contracted H5N8 from migratory birds from Russia. How this happens isn’t clear yet, as poultry are kept inside and wouldn’t have mixed with the wild birds.

Peter O’Hare & herpesviruses – meet the expert – CVR Blog

The guys at the University of Glasgow Centre for Virus Research interview herpesvirologist Professor Peter O’Hare. A great overview of the some of the history, problems and questions associated with those ‘creeping’ viruses of humans. Whilst Peter’s lab do some cool work (this one is a recent favourite – Open Access), he doesn’t include virus latency in his list of big questions in herpesvirology! 😦 For the sake of my fragile little feelings, I’ll assume this is because we’re answering some of the questions, rather than it not being interesting…

Links to go viral – 1st March 2015

This week’s infectious dose:

“Six challenges to stamping out Ebola – Nature”

This article has been pretty popular online this past week. As Ebola lingers on towards the West African rainy season starting in April, we’re running out of time to aggressively end the outbreak once and for all. This article covers some important points, most notably:

  • Aggressive contact tracing can now be pursued in areas with few cases. This tactic is very expensive in terms of money and people power, but is the best way to halt further disease spread. However…
  • …a large proportion of cases in Guinea and Sierra Leone occur in people with no known contact with the sick. In other words, our current surveillance is failing to catch all known cases.
  • Small individual outbreaks are becoming isolated in different geographical regions, requiring aid work to be mobile rather than relying on bringing the sick to centralised centres. However…
  • …it’s going to rain soon. A LOT. This is going to hinder all transport in the region.

The virus isn’t gone yet, and if we let it, it’ll probably come back with a vengeance. I’ve not exhausted the important stuff in this piece. Check it out.

“Measles virus circulating in Ontario is a variant previously unknown to WHO – The Globe and Mail”

The beginnings of an interesting epidemiological detective story here. Recent Measles outbreaks in Quebec can easily be linked to the Disneyland outbreak in the states, but a small cluster of cases in Ontario have come from somewhere else entirely. But where? Measles was eliminated from Canada in the 1990’s, so the virus was likely imported from abroad.

Just goes to show, virus diseases may be extremely rare in your neck of the woods, but in today’s global society, I’d recommend you carry on vaccinating yourself and your family.

“Mail-Order Viruses Are The New Antibiotics – Buzzfeed”

Bacteriophage are extremely cool. Every living thing on the planet has its own viruses, and bacteria are no exception. Despite the advent of antibiotics, doctors in the Soviet Union experimented and developed virus preparations to kill common bacterial diseases. Now with the shadow of antibiotic resistance hanging over the globe, people in the West are turning to these plucky ‘bacteria-eaters’ as our future saviours.

It’s not quite as a simple as that though. Bacteriophage (or phage) therapy requires knowing exactly what bug you’re trying to kill. Why? Because bacterial species are incredibly diverse and bacteriophage are highly species-specific. Think about mice and men – both are mammals, but whilst you could send a cat in to remove your mouse problem, sending in a cat to solve your human problem is going to result in more humans and lots of pictures on the internet.

This article gives a great introduction into the successes and failures of individual Western forays into the exciting world of bacteria-exploding viruses.

The phage are coming! Or are they?