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.

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