Decoded: How Do Vaccines Actually Work?

Vaccines are medicines that train the body to defend itself against future disease.

Unlike other drugs, which we give to some people when they’re sick, we give vaccines to huge numbers of people while they’re well. That’s one reason vaccines go through such extensive testing.

Vaccines work by simulating an infection in the body. This isn’t a real infection, but it teaches the immune system to recognize and neutralize similar pathogens later. If the immune system can stop viruses from replicating, they no longer pose a health risk to the vaccinated individual.

We’ve used this strategy to develop dozens of vaccines over hundreds of years.

People have been immunizing themselves for centuries, starting in India and China. By the early 1600s, people were deliberately infecting children with tiny doses of smallpox, in a process called “variolation.” Variolation was fatal about 2-3% of the time. But it made children immune to the disease, which was normally deadly about 30% of the time.

In 1717, Lady Mary Montagu, wife of the British ambassador to Turkey, introduced the technique to the British medical establishment. She learned about variolation from Ottoman practitioners, and then used it to immunize her own children.

Decades later, physician Edward Jenner learned that British dairy workers had discovered an even safer protective option against smallpox: injecting people with cowpox, a related but less lethal disease that turned out to confer immunity. Jenner tested the theory by injecting an eight-year-old boy with scrapings from a milkmaid’s cowpox blisters. Fortunately, it worked.

When the immune system detects a virus, it makes antibodies to neutralize it. The goal is to block the virus from binding to healthy cells, so it can’t replicate. 

Because pox viruses are related, and use similar binding proteins, cowpox antibodies also ended up protecting the patients from smallpox. And it was much safer to inject patients with cowpox than smallpox.

We no longer immunize people by giving them diseases. Instead, we use vaccines, which work similarly but are much safer.

In the 1930s, researchers discovered they could inactivate seasonal flu viruses using a formaldehyde solution. Formaldehyde itself is toxic. But people injected with the inactivated virus particles ended up developing protection from the flu.

To make a flu vaccine for the wider population, researchers just needed a controlled way to generate lots of virus particles, inactivate them, and then harvest them. 

Based on some early experiments, researchers turned to fertilized chicken eggs, where the viruses multiply exceptionally fast.

The first flu vaccines were released in the 1940s. Even with recent advances in cell culture technology, about 80% of flu vaccines are still made using chicken eggs—hundreds of millions of them, sourced from farms that governments keep secret to protect against tampering.

We can also make vaccines using live viruses, weakened enough so they can’t actually cause the disease. Alternatively, we can use non-infectious pieces of the viruses, or particles manufactured to resemble the pathogens.

Scientists’ latest strategy to fight viruses is using messenger RNA—being deployed for the first time to fight SARS CoV-2, the virus that causes Covid-19. 

To make an mRNA vaccine, experts start by sequencing the viral genome and finding the instructions for how it binds to healthy cells. For SARS CoV-2,  it turns out that it binds using spike proteins that stud the virus’s surface. 

Then, scientists copy and package those genetic instructions and inject them into healthy volunteers, so cells in their body will start producing their own spike proteins (but not attached to any virus). That way, patients create their own blueprint of a critical piece of the virus for their immune systems to learn to identify and neutralize.

mRNA vaccines haven’t been widely used before, mostly because it’s hard to keep artificial  messenger RNA intact long enough to reach host cells. But scientists have overcome that hurdle with new technology (particularly, synthesizing better enzymes to flank the blueprint sequences) and now they’re able to make vaccines incredibly fast. For SARS-CoV-2, they also made changes to the RNA so it produced a very stable version of the spike protein, one the immune system could easily recognize–the natural virus spike kind of wobbles around in a confusing way..

Researchers were able to synthesize RNA for the SARS-CoV-2 vaccine within a week of sequencing the virus’ genome, back in January 2020. That allowed  them to start the first phase of drug trials by March of last year.

Vaccines aren’t miracle cures: they don’t make every individual immune to disease. But what matters is that they work on a population level. 

The key to a successful vaccination program is immunizing enough people to develop so-called “herd immunity,” where most infected individuals can’t spread it to anyone else. This way, over time, fewer and fewer people get infected, ideally until the disease is wiped out entirely.

Diseases still pose a risk as long as there are some  cases anywhere.

This year, we’re witnessing the largest international vaccine development effort ever. SARS-CoV-2 showed how quickly diseases can spread in our globalized world. Now we’re about to find out if the vaccination techniques we’ve developed over centuries are sufficient to meet the challenge: whether we can develop global herd immunity, or if many countries will continue to struggle.

It’s not just about emerging from this pandemic, but about creating a fast and effective strategy to deal with future contagions. They may be inevitable, given how many viruses seem poised to jump from animals to humans.

For now, and the upcoming decades, vaccines will likely be the key to ensuring our collective wellbeing, and perhaps our survival.


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