This week, researchers announced the discovery of a brand new Herpes vaccine. But as with any great break through, we should ask whether it really is worth throwing a parade for ?

Sure, Herpes viruses aren't the most deadly diseases on the planet. You very rarely hear about someone being killed by a cold sore. But they are annoying. Once you get the virus, it never leaves.

Oh, it can go dormant. After you get infected, it can hide away inside your nerve cells, lying in wait. After a long enough time, you might even be able to forget you have the disease. Then one day, when you get stressed out, ill or just have bad luck, the virus can make its comeback. Odds are, you'll be stuck with Herpes longer than the person who gave it to you.

But there is some hope. Researchers have announced that they have created a Herpes vaccine using an entirely new strategy. Exciting huh? Where were this fancy vaccine when I when I was in college and stupid ?


Well, researchers have been struggling with the herpes vaccine for nearly a century. If we want to understand how this new vaccine works, we need to take a look at some of the other attempts to make a Herpes vaccine.

Wait, slow down, how do vaccines work again ?

Your immune system is basically like a police force for your body. Except not really, because it's not like they unjustly target melanocytes.


When the immune system is first exposed to a disease, it's on the back foot. It doesn't entirely know what the disease looks like, or how best to fight it, it has to learn that throughout the infection. For severe diseases, it doesn't get that chance. Which is why we use vaccines, which are there to help the immune system to recognise specific viruses it may encounter in the future. There are lots of ways to do this, but I'm just going to go through the main strategies used against the Herpes virus.

Vaccines made from Dead Viruses

This strategy dates back to the 1920's. The concept is pretty straightforward. Get a sample of live virus, and kill it. Make it so it can't cause an infection.


At first, scientists used chemicals on the virus. For instance, Formaldehyde works by gluing proteins up so they can't move freely.

To the virus, it's like getting encased in Lucite, it's structure perfectly preserved, but ultimately unable to do anything.


But we don't just have to mess with the proteins to stop a virus from working. We can mess with its DNA.

Any skin cancer sufferer can probably tell you that UV light is bad for DNA. The low doses we get from the sun are enough to cause small breaks in DNA, which leads to it becoming damaged. Since this is the instruction manual for cells, wiping out any little of information can be disastrous. Such as the instruction to "stop growing". That one property of UV makes it useful for killing off viruses. High doses of it can annihilate DNA whilst leaving proteins intact.


The problem is that they haven't worked in any properly controlled clinical trial. The thing is, this inactive herpesvirus was too harmless. The immune system encounters viruses and bacteria on a daily basis, most of them living quite happily in your gut. If the immune system reacted to all of them, you'd always be ill. The immune system only pays attention if it believes a certain virus or bacteria is actually causing damage to the body. Otherwise, it ignores them as it would any other piece of debris floating around the body.

Vaccines made from fragments of viruses

Another strategy is to look at the viruses toolbox, and teach the immune system to recognise the specific proteins that the virus uses to infect cells. These proteins are the viruses weapons, and in some cases can be shared between different viruses.


One example is glycoprotein D. This protein is used both by the Cold sore and the Herpes virus. So getting the immune system to recognise this one protein will allow it to react to both of these viruses.

The problem with this kind of vaccine is pretty much the same as above. The immune system will ignore any protein that just happens to be lying around, and dong nothing. So researchers have taken to injecting "Vaccine Adjuvants" alongside the protein. These adjuvants are there the frame the protein for damage it didn't inflict. They get the immune systems attention, which sends cells to see what's up. Glycoprotein D is associated with the adjuvant, and thus makes the immune system's hit list.


Glycoprotein D has made it to clinical trials, with underwhelming results.

Vaccines made from Harmless viruses

The very first vaccine ever used was a less harmful cousin to the deadly smallpox virus . If only we had a less harmful version of the Herpes virus, which we could use as a vaccine. But alas, there is none. But what if we could create one ?


If we rewrite the DNA of a virus, we can change the instructions it uses, making sure it doesn't cause a severe infection. For instance, researchers took out the genes allowing the Herpes virus to go dormant. By effectively removing that instruction from its genetic code, the virus no longer is able to hide from the immune system inside nerve cells. Effectively, this turns viruses into their own vaccines.

So let me explain how this latest vaccine works.

The Vaccine is a mutant virus that can't make Glycoprotein D


Now the virus can't enter cells. Which is great, because it can't reproduce.

Oh, wait, how do we actually grow enough virus to make a vaccine ? We insert the DNA directly into cells grown in a Petri Dish


But when you take the virus outside the Petri Dish, and into a living organism the immune system just ignores this harmless virus.

This is where the scientists did something clever. They went back to the Petri dish, and engineered cells to produce glycoprotein D


These fully armed viruses can enter host cells just fine. But they still can't make Glycoprotein D on their own.


Which means that after this first infection, the virus is harmless. But the damage has been done, and the immune system is now on the case.

Does it work ?

That's the million dollar question. They tested their vaccine in mice. Mice are more vulnerable to this virus than humans. By that, I mean that the Herpes virus can kill mice. Unless we inject them with this mutant virus. They survive when vaccinated.


You may think that's the exciting part, but it isn't. Herpes rarely kills people. Engineering a vaccine to prevent a symptom that rarely shows up in people shouldn't impress you. This vaccine wasn't created to save lives from Herpes, it was created to eradicate it. This is why the researchers went to great lengths to check whether the mice could clear out the virus after being vaccinated. This one graph illustrates the main point. Four days after they were first infected with Herpes, they reduce its numbers so much that its undetectable.

In short, this vaccine candidate looks very promising.

Should I be excited about this vaccine ?

I don't know, that's really up to you. Let's get this out in the open. This isn't a fully fledged vaccine. It's a candidate for a vaccine. It's like we're interviewing the vaccine for a job. We don't know that this candidate can do what we want yet. It looks good so far, but we need further testing, just to be sure. You see, we've been here before.


Nearly twenty years ago, another group created a vaccine using the exact same strategy. Instead of Glycoprotein D, they got rid of Glycoprotein H. It even got through to clinical trials. But it just didn't work.

That doesn't mean that this vaccine won't work. Maybe removing a different protein is enough to make all the difference. Many Herpes vaccines that reached clinical trials never managed clear out the virus completely from the host. We won't know whether this vaccine will work without further testing, but there is hope.

Original study

Herpes simplex type 2 virus deleted in glycoprotein D protects against vaginal, skin and neural disease

Christopher Petro, Pablo A González, Natalia Cheshenko, Thomas Jandl, Nazanin Khajoueinejad, Angèle Bénard, Mayami Sengupta, Betsy C Herold, William R Jacobs Jr


References and Further reading

Status of prophylactic and therapeutic genital herpes vaccines Sita Awasthi , Harvey M Friedman

Herpes simplex virus vaccines David I. Bernstein, Lawrence R. Stanberry

A randomized controlled trial of a replication defective (gH deletion) herpes simplex virus vaccine for the treatment of recurrent genital herpes among immunocompetent subjects, Guy de Bruyn, Mauricio Vargas-Cortez, Terri Warren, Stephen K. Tyring, Kenneth H. Fife, Jacob Lalezari, Rebecca C. Brady, Mohsen Shahmanesh, George Kinghorn, Karl R. Beutner, Rajul Patel, Margaret A. Drehobl, Patrick Horner, Terrance O. Kurtz, Sharon McDermott, Anna Wald, Lawrence Corey