The word “mutation” pops up everywhere in genetics. When we talk about cancer, rare diseases, or superbugs, mutation is there. It’s hard not to think of mutation as something negative, but it really just means change. Mutations are changes in the genetic code of DNA (or sometimes RNA for viruses) that can lead to good, bad, or even neutral outcomes.
For infectious diseases, we’ve talked about how studying these genetic changes can help us understand how a virus is spreading through a community. But knowing how often these changes occur is also an important tool – this time for vaccine development.
When it comes to viruses, the mechanism of mutation is hereditary*, or the kind that occurs between generations. I think of these mutations as “X-Men” type mutations, because they pop up when an organism is “born” but weren’t present in the parent organism(s). This mechanism is different from “Fantastic Four” type, or acquired, mutations that occur because of environmental exposure — like cosmic rays giving you superpowers as was the case for the fictional Invisible Woman – which in the real world is more like UV light from the sun damaging the DNA in your skin cells.
The cellular machinery that copies DNA and RNA doesn’t work perfectly every time. When organisms reproduce or replicate to make more of themselves, we see the same small changes in the genetic code we might after exposure to DNA-damaging events. These small changes (mutations) happen at a particular frequency at each generation — every time two animals reproduce, or a cell divides, or a virus replicates. We call this the mutation rate, and we care about it with viruses because it can give us a lot of useful information. The mutation rate** dictates how often the virus is exploring new combinations that might make it more successful at evading the immune system, which is where mutation intersects with evolutionary success.
According to a 2015 study, HIV, the virus that causes AIDS, mutates very quickly — at the highest rate of any biological entity. This is partly because it copies itself very fast in a very error-prone way. It can also combine versions of itself like “parents” to make a new, even more variable genome. Vaccines depend on training your immune system to recognizesomething it has seen before, so you can imagine why it has been so hard to make a broadly effective vaccine for a virus that has so many changes even within an individual patient — what should the vaccine target? Flu is also a fast mutator, so we need a new vaccine every year to protect against the new strains that have developed. From studying the preliminary sequence data of novel coronavirus SARS-CoV-2, researchers think its genomic mutation rate is lower than for flu. This is good news for a vaccine against novel coronavirus SARS-CoV-2 — the same way a high mutation rate makes it hard to design a vaccine that is effective for many people or across many years, a low mutation rate can make a vaccine effective for longer. If the virus your vaccinated immune system encounters year after year is similar to the original, your immune system will still be trained to respond and so the vaccine is more likely to remain effective.***
As of April 9, 2020, 78 confirmed vaccine candidate projects have entered the global effort, five of which have already moved into clinical development. Many different groups are represented in this effort, from academic research teams to big pharmaceutical companies to government institutes like the US National Institutes of Health, and they are taking a wide variety of vaccine approaches. Canadian contributors include researchers at University of British Columbia and University of Victoria, Dalhousie University and University of Saskatchewan, and BC biotech company ImmunoPrecise.
Footnotes
*To learn more about genetic mutations, there is a great general reference from the US National Institutes of Health: https://ghr.nlm.nih.gov/primer/mutationsanddisorders/genemutation
**Genomic mutation rate means something specific. Usually mutation rates are provided as substitutions per DNA/RNA base per cell which is a very small number that is kind of hard to interpret. It’s also not the only thing that matters, because that same mutation rate for a small viral genome would lead to more changes between generations than for a big viral genome. If we multiply the per base rate by the size of the genome, we get the genomic mutation rate which is the number of mutations an “offspring” has compared to the “parent.” This is important for flu vs. SARS-CoV-2, for example, because they have similar per base mutation rates, but flu has a smaller genome and therefore a higher genomic mutation rate. https://jvi.asm.org/content/92/14/e01031-17
***As with everything related to the novel coronavirus and COVID-19, this represents the best current understanding, which may change as we learn more about the virus.
Additional Resources:
If you want to go deep, here’s a review on viral mutation rates: https://jvi.asm.org/content/84/19/9733
Here is another great read about how seasonal coronaviruses evade the immune system: https://www.nature.com/articles/srep11451
Here is a good resource on how viruses mutate: https://www.cbc.ca/news/technology/faq-how-viruses-mutate-1.780051
WHO draft compendium of vaccine efforts: https://www.who.int/blueprint/priority-diseases/key-action/novel-coronavirus-landscape-ncov.pdf
The Guardian with an excellent piece on when we are likely to have a vaccine: https://www.theguardian.com/world/2020/apr/12/when-will-we-have-a-coronavirus-vaccine
A useful slide deck from Dr. Vaughn Cooper at the University of Pittsburgh School of Medicine about COVID-19 mutation and evolution:https://figshare.com/articles/Evolution_of_SARS-CoV-2/12026913