Antibody Hopes and Vaccine Dreams, Part 2

NCSE Executive Director Ann Reid, who as a research biologist helped sequence the 1918 flu virus, breaks down the steps—and the time needed—for vaccine development.

A scientist working on a vaccine

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Why will it take so long to develop a vaccine against coronavirus?

Let's figure this out together. Let's agree that our end goal is a vaccine that works, is safe, and can be mass produced and administered to hundreds of millions, if not billions, of people. Now, thinking like a scientist, how do you reach that end goal?

But first, a story.

Back in the 1700s, fear of smallpox was so intense that doctors recommended, and many people submitted to, a process called variolation. Doctors took a scraping from an active smallpox lesion and scratched it into the arm of the person hoping to be protected. This did indeed result in immunity to smallpox, at least in those that recovered from the process. Two to three percent of variolated persons, however, developed a case of smallpox serious enough to kill them.

That’s right, people were willing to submit themselves and their children to a procedure that had a 2-3% chance of killing them. That sounds crazy, but given that smallpox had a 20-60% fatality rate and showed up year after year, it was a good bet at the time.

Also of interest, historically, is how the medical community convinced local authorities and their patients that this process worked. When the idea of variolation reached North America, most physicians were skeptical. Only two–Cotton Mather and Zabdiel Boylson–were enthusiastic proponents. When a smallpox epidemic began, they variolated as many volunteers as they could persuade. Then they compared the mortality rate among those that were variolated and those that were not. Mather and Boylston were able to show that the process "worked"–only 2% of their patients died, compared to 14% among the unvariolated.

Still, a 2% mortality rate is not so great. So it was a huge improvement in 1796 when Edward Jenner–having noticed that dairymaids who had been exposed to cowpox were immune to smallpox—had the idea that if you could spread cowpox from one person to another, the recipients would also become immune to smallpox. To test his theory, he took a sample from a dairymaid’s cowpox lesion and scratched it into the arm of a local boy. The boy was briefly and mildly ill and then recovered. Two months later, Jenner took a sample from an actual smallpox lesion and scratched it into the boy’s arm.

Drawing of smallpox and cowpox inoculation

 

Wait, what????!!!! Smallpox had a mortality rate of 20-60%—this was an incredibly dangerous experiment!

But it worked. The boy did not develop smallpox.

Phew.

We are no longer willing to scratch an infectious agent into a child's arm to see if it will bring immunity to a deadlier infectious agent. So what are the steps we follow now? Each step represents a great topic for a group of your students to dig into—I'll just give a general idea and an estimate of how long the step might take.

Step One

The vaccine needs to stimulate an immune response strong enough to prevent reinfection with the coronavirus. (See Antibody hopes and vaccine dreams, Part 1).

How Jenner did it: Tried cowpox, then smallpox.

Time elapsed: Two months.

What we do now:

  1. Show the antibodies block infection in cell cultures in the lab.
  2. Show the vaccine protects animals from infection (note: that means you need to find a good animal model—an animal that is vulnerable to the human disease—and you need a lot of animals.)
  3. Show the vaccine protects people—wait, first you need to know it's safe.

Time elapsed: At least several months, if you get lucky and your first idea works perfectly.

Step Two

The vaccine needs to be safe.

How Jenner did it: He skipped this step.

Time elapsed: None.

What we do now:

  1. Test the vaccine in small number of healthy volunteers. If there are no side effects …
  2. Test the vaccine in a larger number of more diverse volunteers. If there are no side effects …

Time elapsed: At least a couple of months per round.

Step Three

Show the vaccine protects people.

How Jenner did it: tried cowpox, then smallpox.

Time elapsed: Two months.

What we do now:

  1. Identify a group of people who have not contracted the virus before (see Antibody hopes and vaccine dreams, Part 1) but are at high risk of being exposed (question for students: why is it important that they're at high risk?)
  2. Give half of this group the vaccine.
  3. Wait.
  4. Count how many people in each group got sick. Also check to see who has developed antibodies.

Time elapsed: At least three months. Because you're waiting for natural infections to develop, you have to wait until many people in the group have encountered the virus. It can be up to two weeks before symptoms develop.

Ideally you would then do several more trials like this, with larger and larger groups of more diverse people in both low- and high-risk situations. But this is an emergency. Arguably, we might decide we can't wait for that.

Step Four

After completing steps one through three, you have to be able to manufacture and administer the vaccine in vast quantities. To substantially block transmission of the virus, it would be ideal to get herd immunity above 90% (or about 300,000,000 Americans and 7 billion people worldwide today).

How Jenner did it: He and other doctors could get fresh vaccine from smallpox patients. By the late 1800s, smallpox vaccine was being produced commercially.

Time elapsed: No time elapsed, or 100 years, depending on how you count.

What we do now: Engineer a mass production process with rigorous quality control. The figure above shows the steps. Bottom line: extremely complicated.

Time elapsed: Six to 36 months.

If you add up the time elapsed for all four steps with regard to what we do now—bearing in mind that the time estimates are best-case scenarios—you end up with a bare minimum of 18 months to develop a safe, effective, mass-produced vaccine. That's just what it's going to take, unless you want to go back to scratching infectious agents into kids' arms.

NCSE Executive Director Ann Reid
Short Bio

Ann Reid is the Executive Director of NCSE.

reid@ncse.ngo

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