Vaccines are drugs that train the body to defend itself against future diseases.
Unlike other drugs that we give some people when they are sick, we give vaccines to large numbers of people while they are well. This is one of the reasons vaccines go through such extensive testing.
Vaccines simulate an infection in the body. This is not a true infection, but it does teach the immune system to recognize and neutralize similar pathogens later. If the immune system can stop the replication of viruses, they no longer pose a health risk to the vaccinated person.
We have used this strategy to develop dozens of vaccines over hundreds of years.
People have vaccinated themselves for centuries, starting in India and China. In the early 17th century, people intentionally infected children with tiny doses of smallpox, which was known as “variolation”. The variolation was fatal in about 2-3% of the cases. But it made children immune to the disease, which was usually fatal about 30% of the time.
In 1717, Lady Mary Montagu, the wife of the British Ambassador to Turkey, introduced the technique to the British medical establishment. She learned variolation from Ottoman practitioners and then used it to immunize her own children.
Decades later, doctor Edward Jenner learned that British dairy workers had discovered an even safer option to protect against smallpox: injecting cowpox, a related but less fatal disease that conferred immunity. Jenner tested the theory by injecting scratches from the cowpox blisters of a milkmaid into an eight-year-old boy. 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 that it cannot replicate.
Because smallpox viruses are related and use similar binding proteins, cowpox antibodies also protected 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 that work similarly but are much safer.
In the 1930s, researchers discovered that they could inactivate seasonal flu viruses with a formaldehyde solution. Formaldehyde itself is toxic. But people injected with the inactivated virus particles eventually developed protection against the flu.
To make a flu vaccine for the general public, all the researchers needed was a controlled way to generate lots of virus particles, inactivate them, and then harvest them.
Based on some early experiments, the researchers turned to fertilized chicken eggs, where the viruses multiply exceptionally quickly.
The first flu vaccines were released in the 1940s. Even with recent advances in cell culture technology, roughly 80% of flu vaccines are still made from chicken eggs – hundreds of millions of them come from farms that governments keep secret to protect them from tampering.
We can also make vaccines with live viruses that are so weakened that they can’t really cause the disease. Alternatively, we can use non-infectious parts of the viruses or particles that are made to resemble the pathogens.
Scientists’ latest strategy to fight viruses is to use messenger RNA, which is being used for the first time to fight SARS CoV-2, the virus that causes Covid-19.
To make an mRNA vaccine, experts first sequence the viral genome and find instructions on how it binds to healthy cells. SARS CoV-2 turns out to bind using spike proteins that examine the surface of the virus.
The scientists then copy and package these genetic instructions and inject them into healthy volunteers so that the cells in their bodies begin to produce their own spike proteins (but which are not linked to a virus). In this way, patients create their own blueprint of a critical part of the virus so that their immune systems can learn to identify and neutralize themselves.
mRNA vaccines have not been widely used, largely because it is difficult to keep artificial messenger RNA intact long enough to reach host cells. But scientists have overcome that hurdle with new technology (specifically, synthesizing better enzymes to flank the blueprints), and now they can make vaccines incredibly quickly. For SARS-CoV-2, they also made changes to the RNA, creating a very stable version of the spike protein that the immune system could easily detect – the natural virus spike species wobbles around in confusing ways.
As early as January 2020, the researchers were able to synthesize RNA for the SARS-CoV-2 vaccine within a week of sequencing the virus genome. This enabled them to begin the first phase of the drug trials in March of last year.
Vaccines are not a panacea: They don’t make everyone immune to disease. What is crucial, however, is that they work at the population level.
The key to a successful vaccination program is to immunize enough people to develop what is known as “herd immunity,” where most infected people cannot pass it on to others. In this way, fewer and fewer people become infected over time, ideally until the disease is completely eradicated.
Illness is still a risk as long as there are cases somewhere.
This year marks the greatest international vaccine development effort ever. SARS-CoV-2 showed how quickly diseases can spread in our globalized world. Now we are going to find out if the vaccination techniques we have developed over centuries are sufficient to meet the challenge: whether we can develop global herd immunity, or whether many countries will continue to have problems.
It’s not just about getting out of this pandemic, it’s about developing a quick and effective strategy to deal with future contagions. They can be inevitable considering how many viruses are ready to jump from animals to humans.
For now and decades to come, vaccines are likely to be key to ensuring our collective wellbeing and perhaps our survival.