Whooping cough, vaccines, and leopard-print hats
This week's blog is in celebration of the publishing of an article that I helped with during the first internship of my M.Sc.! I wanted to share this article, but also explain what it means for science and for the public.
The research in this article is all about Bordetella pertussis, the bacteria that cause whooping cough. Whooping cough is another of the diseases that many readers will not be personally familiar with. This fact is a testament to the success of vaccinations!
In the mid-19th century, very successful vaccination campaigns almost eliminated cases of whooping cough in the rich countries in North America and western Europe. The actual disease caused by whooping cough is just how it sounds - a nasty cough that gets so bad that people 'whoop' when they try to inhale air after the coughing spell. Usually, healthy adults and older children recover from whooping cough, but infants are the hardest hit. Very young children and newborns can develop rather severe side effects or even die from infections with Bordetella pertussis.
In reading that last paragraph, maybe your eye caught on the bit about very successful vaccination campaigns. "Well," you might have thought, "In that case, why is more research necessary? We've tackled this bug!" Unfortunately, Bordetella pertussis infections are re-emerging despite the still high vaccination rates. In other words, even though we are vaccinating, this bug is beating our vaccinations.
Before we go further, it's important to understand how the vaccination against whooping cough works. The one that we currently use is called the "acellular pertussis" vaccine. This means that there aren't actually whole bacterial cells in the fluid that is injected. Instead, there are broken up bits of the bacterium - but very carefully selected bacteria bits. These bacterial bits need to be present on almost all of the bacteria that are going around. You can think of this as a sort of hunt for the wanted bugs - just like with the flu vaccine. If your immune system is the body's police force, a vaccine can notify the police to keep an eye out for bacteria wearing green pants and a leopard-print hat. If all the Bordetella bacteria out and about are wearing that same wacky outfit, then your immune system will be pretty good at identifying and tackling them. But, a problem arises if the Bacteria drop the leopard print hat: it makes the immune system less effective at finding them. This change of bacterial bits is exactly what we think Bordetella may have done, to permit its re-emergence.
So, what can we do to fight back? To answer the bacterial costume change, we need to update the 'wanted poster': we need to update the vaccine. That way, we can teach our immune system to recognize the new-and-improved Bordetella strolling about. The first step in doing this is to find out what these updated bacteria are wearing, and what exactly they are using their costumes for.
One of the bacterial bits that a lot of Bordetella pertussis bacteria are carrying around these days is the Vag8 protein – full name Virulence Associated Gene 8, but that's quite a mouthful so it goes by Vag8 for short. Dutch researchers have already found out that vaccinating mice with Vag8 protects them from infection with Bordetella pertussis, which is a sign that Vag8 might work well for vaccination in humans, too. However, we have to be very, very careful with updating vaccines. Before we add in any new bacterial bits to a vaccine, we want to know exactly how those bits work and what they can do in the human body, to avoid causing any harm.
So, what does Vag8 get up to, then? Elise Hovingh, the lead author on the paper published today, had already shown how Vag8 messes with a subset of the human immune system called the complement system. This system helps target invading bacteria for destruction early in the immune response - i.e. within the first hours to days of being infected. Interestingly, the proteinaceous machine within the complement system that Vag8 specifically targets, called C1-inhibitor, can also wear another hat. C1-inhibitor is also involved in regulating the contact system, a part of the system responsible for blood coagulation, or the thickening of the blood into clots. In our paper that was published today, we proved that Vag8 can indeed also mess with the contact system by targeting C1-inhibitor.
Why is this research important? It turns out that the activation of the contact system is linked with coughing! There is very limited research on this link between contact system activation and coughing, but it's there nonetheless. Therefore, Vag8 might be one of the things at the root of the terrible, whooping coughs of whooping cough. This discovery is also important to consider before any updating of the whooping cough vaccine. If Vag8 were directly injected, it might actually give people the coughing symptoms. To avoid this, Vag8 would have to be modified a bit - for instance by cutting a bit of it off - before including it in a new vaccine. So, to sum up, there is a lot more work to be done before the vaccine will be updated – but that's just how science goes!
Until next week - don't forget to vaccinate!