We’re all watching for a vaccine for COVID-19, which sadly probably won’t come until mid to late 2021 if all goes well. (Most likely, what will get us out of having to do social distancing will not be a vaccine but a reliable treatment).
Vaccines have been controversial of late, with the anti-vax movement causing its various issues. But vaccines remain one of our biggest medical breakthroughs as a species.
What was the First Vaccine?
Most of us know the story of the first vaccine. Edward Jenner, in the 18th century, noticed that dairy workers did not get smallpox as often as the general population.
It turned out that a much milder disease carried by cows, cowpox, was so closely related to smallpox as to be what we now call cross-reactive. Antibodies to cowpox stopped smallpox.
Jenner hunted down a dairy maid with cowpox and took material from her lesions, which he then used to inoculate a child. He then, in steps which would be utterly unethical today, tried to give the child smallpox and failed (If you have heard the words “human challenge trials” in relation to COVID-19 vaccination, this is exactly what they mean). His method became known as vaccination…from the Latin for cow.
Vaccination had begun. Except, this was not the beginning.
Inoculation or Variolation
Before vaccination, we had inoculation. Inoculation against smallpox involved intentionally introducing the virus subcutaneously. The layer immediately under our skin has a very strong immune response (at least one COVID-19 vaccine candidate is intended to be introduced subcutaneously), and the technique resulted in giving the person an extremely mild disease that left them immune to smallpox.
It was not without its risks. Some inoculated individuals did go on to develop full-blown smallpox. In some areas, thus, it was common, in others discouraged. In fact, in Norfolk County, Virginia, a doctor’s house was burned down because people were so mad he was practicing inoculation. There was about a 1 in 1,000 fatality rate, but that compares to the 35% fatality rate not uncommon in outbreaks of smallpox.
We now most often use the word “inoculation” as a synonym for vaccination. The alternative term, “variolation” has fallen out of use.
We no longer do variolation in the traditional sense, but one of the tactics being used against COVID-19 is the rather more sophisticated version of isolating antibodies from recovered patients and cloning them in a lab. This is generally a faster development timeline than a vaccine, but provides less certain protection.
Vaccines Since Jenner
We no longer vaccinate people by giving them a milder, related disease. In most cases there is no such disease to use, although cross-reactivity is a known thing that’s helpful in many cases. Cross-reactivity is why getting your flu shot will make even strains that are not in the vaccine milder. COVID-19 appears to be cross-reactive with SARS, and there’s some evidence it may be cross-reactive with other human coronaviruses. Please don’t assume you’re protected because you had a cold, though — this is far from confirmed and most colds are not coronaviruses.
But there have been many developments since. Louis Pasteur is better known for pasteurization, but he developed vaccines for cholera and anthrax (both bacteria; yes, you can vaccinate against bacteria. Did you get your tetanus shot?). The cholera vaccine was the first live attenuated vaccine and the anthrax vaccine was an inactivated vaccine. This was the start of creating vaccines in the lab by playing with viruses and their genetic code.
In the 1950s we started to develop viral tissue culture methods, which made it much easier to create vaccines. This led to the Salk and Sabin polio vaccines and then to vaccines against measles, mumps and rubella.
There are now four main types of vaccine:
- Live attenuated vaccine — this is a strain of the virus bred to not cause severe illness while still creating an immune response. Examples include MMR (measles, mumps, and rubella) and chickenpox.
- Inactivated vaccine — take the virus, “kill” it and then show it to the person’s immune system. These generally don’t provide as good protection and you usually need boosters. Examples include polio and your regular flu shot.
- Subunit, recombinant, polysaccharide and conjugate vaccines. Those various mouthful terms all refer to the same thing: You take part of the virus and show it to the immune system. These vaccines are better for people with weak immune systems who might get sick from a live attenuated vaccine. Like inactivated vaccines, you generally need boosters. Examples include whooping cough (now generally given in a combination with diptheria and tetanus) and shingles.
- Toxoid vaccines. These are a bit of a different animal. Instead of targeting the germ, you use a toxin produced by the germ and program the immune response to target it. These vaccines can give protection to diseases that don’t give natural immunity. This is your tetanus vaccine.
For COVID, all of the first three approaches are being worked on, but we’re also working on what might be the next stages in vaccine technology, and they’re pretty exciting.
Vaccines of the Future
Before COVID-19, and likely after, the vaccine holy grail was the universal flu vaccine.
Flu shots are a tricky thing. We have all at least known somebody who got the flu shot then still got the flu. Sometimes it isn’t the flu, but is a “flu-like” virus such as enterovirus or parainfluenza. But sometimes it is. Every year, we play Flu Shot Roulette. The flu shot contains the four strains epidemiologists think are going to be most common in your area for that winter. Sometimes they make a better guess than others. This doesn’t mean you shouldn’t get your flu shot, but does explain why it doesn’t always work. Oh, and then it wears off.
The idea of a single shot that would protect you against all or most strains of the flu has been worked on for years. Ideally it would even grant some protection against the next epidemic flu (usually a zoonotic strain). Unfortunately, it’s proved to be a tricky grail to track down indeed.
But we do have candidates, using multiple techniques. One approach is to try and get the immune system to respond to a specific protein stalk produced by almost all flu viruses. Another is to induce a T cell response against internal proteins. Will we have one? Eventually, but vaccine development normally takes years; and this was no doubt slowed by the, you know, global pandemic.
That aside, we’re also working on new ways to create vaccines, and here are some fascinating possibilities:
- Gene-based vaccines. These vaccines trick your own cells into producing tiny quantities of viral protein to trigger an immune response. DNA vaccines are being worked on for Zika and COVID-19 and Moderna’s coronavirus vaccine candidate, mRNA-1273, is an RNA vaccine. No vaccine using this technique has been approved. We don’t know for sure if it’s safe and works, but it might produce a longer-lasting immunity than either natural immunity or other vaccines.
- Friendly virus vaccines. And we’re back to cowpox! Except better. A friendly virus is one which is harmless to humans. Insert benign genes from the virus you want to vaccinate against and then give the person the friendly virus. This strategy has already been used once with success, for ebola.
Ironically, it’s not impossible that we’ll contain COVID-19 or some other disease…with the same technique Jenner pioneered. We just know how to do it better now.