Tracking where vaccines go in the body

Vaccines are very much the talk of the town at the moment as the world strives to protect populations everywhere against the new coronavirus. And although we broadly understand that, when we immunise someone, the material we inject gets carted off to lymph nodes where it’s presented to the immune system and provokes the production of protective antibodies and T cells, the more fine-grained detail of what’s really happening isn’t clear. But now Beth Tamburini, at the University of Colorado, has developed a way to use special DNA tags that she can couple up to the antigens in a vaccine and then follow where the antigens go by looking for the DNA tag…

Beth - We were looking at different vaccination strategies, some of which we knew were better than others. And we were asking whether or not we could track these vaccines by taking this sort of molecular tag and conjugating it to a protein antigen, which is just a piece of pathogen we can inject into the body to make the immune system become educated that that is something that it should respond to.

Chris - And this therefore gives you an insight into when you put a vaccine into the body where it goes, but critically also how long it hangs around for, and who's looking at it?

Beth - That's right, because we can look at different time points after vaccination and tell whether or not the tag is still there.

Chris - What tags did you use and how do you make sure that they don't just fall apart?

Beth - We used DNA and we had to protect the DNA tag using these different types of bonds between the base pairs of the DNA. So that would protect the tag from degradation in the body.

Chris - Essentially, then, we've got, what, a protein, which is the vaccine molecule, and you've got coupled up to it, a hunk of DNA on the side, which is like a unique identifier, like a barcode effectively saying, this is the vaccine molecule.

Beth - That's correct.

Chris - And you can then go back in and read that DNA. So, you know, specifically it's the DNA, not just random DNA from around the body, that is the DNA corresponding to that vaccine molecule?

Beth - Yes, because it has this unique barcode and we can manipulate the barcode so that we can track different barcodes throughout the body. If we were looking at say multiple different types of vaccinations or boosting strategies.

Chris - So you've made a cluster of, of these things. What is it telling you? What have we learned through, through having this now quite neat tagging system, then that enables you to see where the vaccines go and how long they're hanging around.

Beth - We can use this vaccine and we inject it under the skin. And then we ask where the vaccine goes. And we're most interested in the lymph node, which is the place where the immune system becomes educated. There are different cells within the immune system that live within the lymph node. And so we can ask which cell types recognise this part of the pathogen and how they are responding and how they are holding on to the protein, antigen, or pathogen that we've tagged.

Chris - What did we learn? Because obviously that has been a central tenet of immunology for decades. That's how it works. That things get presented to the immune system in lymph nodes. And that's how we, we create the immune response. And that's why your glands swell up when you have an infection, let's be honest. So what did we learn from this that we didn't know before?

Beth - So what we've learned is that protein antigen that we've injected with the barcode stays in the lymph node for a longer period of time than we had anticipated. And this, we had some evidence for, from other studies, but we had some difficulty with tracking the antigen in the previous studies. With this new technique, the tag is actually quite a bit more stable. So we could detect vaccine antigen for a longer period of time and detect it in very small amounts. So the specific subset of cells actually could hold on to this protein antigen for over a month, which is far longer than the immune system takes, which is about a week, to respond and clear any pathogen.

Chris - And if we compare and contrast between vaccines we know produce a very potent response and those that are less good, is there any difference in how long the antigens from those vaccines hang around in the lymph nodes? Could that account for why some vaccines are really good and some are less good?

Beth - Yes. that is something that we're really trying to understand, which is why we're studying, how long the protein antigen stays in the lymph node. Based on our studies, it does appear that if you have the protein antigen staying within the cell type in the lymph node for a long period of time, it is beneficial if you become infected with the same thing later on, compared to if you didn't have the protein antigen there.

Chris - So we could use your technique then to investigate for the optimum latency in the lymph node, as it were, of whatever the stimulus is for the immune system to find something that will give a really good dwell time in the lymph node of that stimulus to also then translate into a really good memory potentially? So it could be used to sort of goal seek for superior vaccines of any type?

Beth - Yes, that is the goal is to try to understand what different types of vaccines cause this process of protein antigen retention, and how we can manipulate it so that we can make better vaccines.