Virology 101: Coronavirus, vaccines and treatments
A primer on the quest for a way to neutralize the SARS-CoV-2 virus
The race is on to find a vaccine against SARS-CoV-2, the novel coronavirus that has unleashed the COVID-19 pandemic.
More than 100 different vaccine candidates are in development around the world, but even that level of global attention is no guarantee of success. To date, no vaccines have been developed against other members of the coronavirus family, such as the original SARS (severe acute respiratory syndrome) that hit Canada in 2003.
“Some viral families are very challenging to generate vaccines against,” said McMaster University professor Karen Mossman, a virology expert in the department of pathology and molecular medicine.
The cat-and-mouse interactions between viruses and the immune system are incredibly complex.
Here’s a primer on the quest for a way to neutralize the COVID-19 virus:
How does the novel coronavirus infect the body?
A virus is a piece of genetic material covered with a protein coating. In the case of the coronavirus, the genetic material is made up of RNA (ribonucleic acid), the sibling of DNA (deoxyribonucleic acid), which carries the genes in the nuclei of our cells.
On the surface of the virus are protein spikes, which are like a key that matches up with a lock on the outer membrane of a cell. When the key fits into the lock, it allows the virus to slip inside the cell.
Once inside, the viral genetic material spills out and the virus takes over some of the internal machinery of the cell to make copies of itself — hundreds to thousands to even tens of thousands of copies.
New protein coatings are produced to wrap up the genetic copies. Then the virus takes over the cell’s packaging machinery so the copies are shed back out through the cell membrane. The copies then circulate looking for new hosts to invade.
The COVID-19 virus has a lot of genes, said McMaster professor Dawn Bowdish, who is part of the McMaster Immunology Research Centre.
“It’s kind of a giant,” said Bowdish, meaning it takes longer for the virus to be assembled and longer to be expelled.
“That could be why we see that there’s such a long period of viral shedding with this virus,” she said. “We find people who have been infected are often shedding some of that virus for days if not weeks.
“That slow simmer is probably giving the virus time to get deep into the lungs and infect lots of different cells there.”
How would a vaccine work?
When something foreign enters the body, such as a virus or bacteria, the immune system responds first by building unique bits of protein called antibodies that act as detectors. Every different virus or bacteria will cause its own specific antibodies to be produced.
Antibodies bind on to a very specific part of the invader, sending up a red flag. This starts a chain of events that will unleash defenders that are sent to look for any of the invaders that are waving the red flag signalled by the antibodies and destroy them.
It’s also possible to have the immune system respond to cells that are infected with a virus because those cells will exhibit a red flag on their surfaces that tells the defenders to destroy them.
A vaccine is a way to introduce into the body the key parts of the virus that send up the red flag to the immune system. The challenge with a vaccine is to produce something that’s close enough to the virus that it will stimulate a response from the immune system but not something that’s going to cause an infection itself.
The advantage of a vaccine is that the antibodies give the immune system a memory so that any time the same virus enters the body, it will be recognized as a foe and destroyed before it can cause damage.
How will a COVID-19 virus vaccine work?
The vaccine candidates in development now are trying to figure out which part of the outer coating of the virus is going to provoke an immune response strong enough to prevent an infection from taking over.
The focus of vaccine efforts is on the spike protein of the coronavirus.
“But the spike protein is a very, very big protein,” said Mossman. “Antibodies only recognize a very small part of any given protein.”
The goal now is figuring out “what part of the spike protein would be most effective to block,” Mossman added.
That’s why there are so many trials underway.
“That’s a great comfort to me because I’m hoping with so many different approaches being tested somebody’s going to get it right,” said Bowdish.
The tricky part is that viruses are constantly mutating, which means the proteins on the outside can change. Some parts of the virus tend to mutate more than others.
The challenge for a vaccine is to target a part of the virus that isn’t mutating so the body will keep seeing it as a foreign invader in the future.
What about using the blood of infected people who have healed?
There are trials now going on to see if the plasma from infected people might have a protective effect on people who haven’t yet been infected with the COVID-19 virus.
The theory is that infected people will have produced antibodies to the virus that keep circulating in the blood. If you transfer those antibodies into a healthy person, it could prime the pump so the immune system will kill off the virus once it enters the body.
The question is whether or not the antibodies alone are enough to provoke a strong immune response. If they are, the chances of making a successful vaccine that targets part of the virus are improved.
If they aren’t, it means a vaccine will have to target cells that are already infected with the virus and the success rate historically for that type of vaccine is much lower.
Using the plasma of previously infected people won’t be a substitute for a vaccine in any event. The antibodies can’t be mass produced and the plasma from one recovered COVID-19 patient might only help two other people. On top of that, blood types have to be matched.
What about a treatment instead of a vaccine?
In general, antiviral treatments for people already in the midst of an infection have been difficult to produce. One big reason is because viruses can mutate rapidly.
“The more pressure you put on a virus, the more chance a mutation will persist that allows the virus to get around that pressure,” said Mossman.
One big antiviral treatment success has been HIV. The development of a cocktail of drugs has turned HIV from a death sentence to a manageable chronic disease.
“It’s harder for a virus to mutate around three or four different modes of action,” Mossman said.
The best chance of success for a COVID-19 antiviral treatment might also be a cocktail of different drugs.
A cocktail treatment for COVID-19 could also help when the next deadly coronavirus epidemic comes along some day.
“We’re naive if we think it’s not a possibility,” Mossman said.