By Alexandra Becker

Ever since the U.S. Food and Drug Administration (FDA) granted Emergency Use Authorization to the first COVID-19 vaccine last December, the research, development and science behind vaccines has become a household topic like never before. But vaccines themselves date as far back as the late 1700s when a physician from Gloucestershire, England created an experimental therapy during a smallpox outbreak in an attempt to save a little boy’s life. As the story goes, Dr. Edward Jenner took fluid from cowpox lesions and scratched a small amount into the eight-year-old’s skin; the boy became mildly ill but then recovered and survived the deadly outbreak.

It was one of the earliest experiments to use exposure to a virus as a way of harnessing the immune system to create antibodies. Since then, scientists have developed vaccines for some of the world’s most contagious and dangerous diseases—including one that, thanks to widespread distribution, lead to the eradication of smallpox across the globe.

But why do vaccines vary so much in type, dosage, and administration schedules? For example, why do we get a vaccine against seasonal influenza each year, a vaccine against tetanus every 10 years, and yet the measles vaccine we receive as children lasts a lifetime?

“There are a couple of different components to this answer, and one of them is the differences between viruses,” explained Dr. Linda Yancey, MD, an infectious disease expert with Memorial Hermann Health System. “We often talk about viruses as if they are the same thing, but they are as different from one another as cats are from asparagus. Some viruses are relatively huge while others are tiny in comparison, some use RNA while others use DNA—they are very, very different organisms.”

Yancey said that for vaccines that “last a lifetime,” which include vaccines for measles or hepatitis B, the viruses themselves tend to be uniform when they replicate.

“They replicate very faithfully, so if you have hepatitis B, every hepatitis B virus in your body looks identical,” Yancey said. “The same with measles. They are very good at replicating themselves without error, and that is a huge benefit for us, because it means that once you get antibodies against one hepatitis B or measles virus, you have immunity against every hepatitis B or measles virus you are ever going to encounter.”

Those types of viruses, Yancey said, are on one end of the spectrum. On the other end are viruses that are widely variable—and thus harder to attack with an across-the-board vaccine.

“Viruses like HIV or hepatitis C tend to be very, very small, and the smaller a virus is, the worse its machinery works,” Yancey said. “When hepatitis C or HIV is replicating, it makes a lot of mistakes, so instead of all of the HIV or hepatitis C viruses in someone’s body being identical, they are all slightly different. That’s why, 40 years after the discovery of HIV, we still don’t have an HIV vaccine.”

Influenza would likely lie on this same end of the spectrum, but the nature of the virus itself is in a category of its own.

“The reason we have to get the flu shot every year is that the influenza virus is able to shuffle its chromosomes around in a way that most viruses cannot,” Yancey said. “Viruses like hepatitis C, HIV and coronavirus have a single chromosome—all of their genetic material is stored on one strip of either DNA or RNA—but the influenza virus has seven different chromosomes.”

Yancey added that if two strands of influenza infect one person or one animal, they have the ability to shuffle their genetic material and create a completely new strain.

“This actually happens on a very regular basis, and that’s why, every year, we have to come up with a new flu vaccine depending on the strains currently circulating,” Yancey said, adding that there is a saying in virology that goes: If you’ve seen one influenza season, you’ve seen one influenza season.

Yancey noted that researchers are currently working to develop an mRNA vaccine for influenza, which could point to a more effective vaccine due to logistics related to manufacturing and timing.

“Right now, we are speculating what strains will be circulating nearly a year in advance so that we can create enough flu vaccines ahead of flu season,” Yancey said. “With mRNA vaccines, those can be developed and manufactured more quickly than the current technology, which means we can wait until just a few months before flu season and get a more accurate idea of the composition of the strains that will actually be making people sick that year.”

Sitting between the two extreme ends of the spectrum lies a host of other diseases including pertussis, also known as whooping cough, and tetanus, both of which are technically a type of bacteria.

“Because of the way pertussis and tetanus are shaped, it is more difficult to generate immunity against these, even though they are pretty faithful in their replication,” Yancey explained. “There are no great vaccine targets that are easily accessible, so immunity doesn’t last for too long, which is why we recommend getting those vaccines every decade or so.”

On the subject of shape, Yancey noted that the coronavirus has an ideal composition for the development of a successful vaccine.

“It has the spike protein on the outside of the virus, so the immune system can get to it quickly—it’s the first thing that interacts with human cells,” Yancey said. “It’s as good a vaccine target as you could possibly hope for.”

Yancey added that the coronavirus is also consistent in its replication inside the body, which points toward an optimistic future for getting the pandemic under control—for good.

“To put things into perspective, if we had measles running through the world the same way we have COVID-19 right now, measles would be evolving and creating variants, too,” she said. “The reason we don’t see variants in mumps or measles is because most of the planet is vaccinated against them. That’s good news for the future, because if we can get enough of the world vaccinated against COVID-19, we can slow the production of variants until it virtually comes to a stop.”

Someday, she added, with enough global vaccination, the COVID-19 vaccine may become one that lasts a lifetime.

“We have the science to do this, we just need everyone to get vaccinated,” Yancey said.