This week, we asked our experts, Susan and Lindsey, to weigh in on concerns that COVID-19 mutations might derail plans for a vaccine. Their conversation is given below and it’s an excellent look at not only the nuances of viral mutations in the context of the current pandemic but also viral mutations in general.
Because (full disclosure) this conversation gets a little technical, we’ll break from tradition and give you the bottom line first: mutations in SARS-CoV-2, so far, appear to be too slow to drive higher death or infectivity rates. Generally, viral mutations that suddenly and dramatically increase the infectivity and lethality are rare. And better yet, vaccines tend to target the parts of viruses that remain the same across mutations.
A quick word on the science: genes (DNA, RNA) tell cells to make proteins. Different genes tell cells to make different proteins (in other words, the specific protein that the cell makees depends on the genes being used). A mutation is a random change in genes that could affect the final protein or have no effect at all, depending on the type of mutation and where in the gene it occurs. Changes in that final protein structure are what we’re concerned about—i.e. the fear would be that the virus SARS-CoV-2 mutates so it becomes deadlier and/or more contagious.
Lindsey: I'm not sure if the same is true for Susan but COVID-related news headlines generally feel like Groundhog's Day to me: every few months similar studies/abstracts get picked up and we have to go through the same process of emphasizing that facts on the ground haven't changed much. Mutations have felt a bit like that to me.
Susan: Yeah, the mutation stuff goes around constantly. If the virus was mutating to become more deadly we should see that in deaths increasing. That’s obviously the biggest worry. The mutating to avoid vaccines is obviously a worry but most vaccines are protein or mRNA [related to the virus’s genes] based right now. And mutation usually only happens with selection pressure so we don’t expect to see mutation until large numbers of people are vaccinated.
Lindsey: Yeah, it’s wild to me how slowly this virus seems to be changing: an average of two mutations per month means we’re looking at, what, 11 months out from the Wuhan outbreak an average difference of 22 nucleotides [DNA/RNA parts]? And the whole genome [totality of the virus’s genes] is massive so you’d have to have an extremely unlikely event occur to have a single nucleotide change [a single, small change in the virus’s genes] make a macro difference [in the overall structure of the virus] by chance. It’s 2020 so I won’t say “never” but…
Susan: Yeah, it’s actually pretty slow and it has to mutate in the right epitopes [spots where our body’s immune system attacks foreign invaders] to cause immune evasion and since we are not using single peptides [single, specific parts of the protein] for the vaccine, the vaccine will likely still work as long as the viral mutations don’t occur in the specific locations targeted by the vaccine.
Lindsey: So would that be a unique concern of the protein-based vaccines? I’m thinking the ones based around the spike protein [a key protein that SARS-CoV-2 uses to invade cells] obviously...in my head in theory the spike could change enough to make those ones less effective.
Susan: If you’re vaccinating with the whole spike, it’s composed of hundreds of peptides [protein parts] and everyone responds slightly differently. The spike protein changing enough to cause a different strain is comparable to the flu changing every season, but the spike protein can’t change too much because it would change the functionality of the virus. But we also know that there is cross-reactivity [the ability of the body to still attack even when there are changes in virus structure] so even if the virus changes then there may still be immune responses.
Lindsey: How is the spike vaccine hundreds of peptides? I picture a fully assembled spike in my head? I take it…that is not the case.
Susan: So the spike protein [again, the protein that the virus uses to invade cells] is composed of strings of amino acids [protein parts] that form peptides [bigger protein parts] and fold into a protein structure. When the spike protein enters the cell it gets broken down into peptides [protein parts again] which then get presented to the immune system. So when evasion by the virus happens, it’s these individual peptides that can’t bind.
Lindsey: Essentially you’d need a really substantial change, not just in one virus but in one that goes population-wide to evade most of our vaccines.
Susan: The dominant responses are usually shared (public) and there are also individual (private) responses. So if you are worried about the virus becoming more lethal it’s one thing, but if you are worried about the vaccine then it would need to be very different since the whole spike is used, we’re not biasing the response to one peptide [one protein part of the SARS-CoV-2 virus].
Immune system puts pressure on virus; virus evolves to escape immune system; immune system responds again. It happens at both an individual level and a population level. So the spike protein would have to change dramatically to make it evade the immune system.
Lindsey: And there’s speculation that a nonsense mutation in SARS the original may have helped slow its spread [as opposed to speed it up, as one might naturally think]. So basically we don’t even frame mutations correctly given the likelihood of the effects they will have.
Susan: Yeah, so viruses have evolved to be efficient, so when they mutate it is likely to be detrimental [to their ability to be more contagious or deadly]. And the conserved sequences [the bits that remain constant across mutations] tend to be what we target for vaccines.
Lindsey: That’s what they’re trying to go after for with, say, a universal flu vaccine.
Susan: Yeah, we all worry that viruses mutating is like in the movies—the virus mutates and becomes resistant or lethal. It’s not like that doesn’t happen, but it’s rare.