Will Virus Mutations Threaten COVID-19 Vaccines?
We don't yet know whether new variants of the coronavirus may impede vaccines’ efficacy. But they shouldn’t change anything about our approach to public health.
On Dec. 8, the United Kingdom became the first Western country to begin inoculating its citizens against the coronavirus, with Canada and the United States close behind—a sign for many that there may, in fact, be a light at the end of the tunnel after a year of public health catastrophe. To date, COVID-19 has caused more than 79 million infections and 1.7 million deaths worldwide, harrowing numbers by any measure. For those who have weathered or thus far avoided infection, COVID-19 has turned life as we know it on its head.
Yet despite that hope—or, rather, in order to preserve it—it’s important not to abandon pandemic protocols like mask-wearing and physical distancing too soon: Just because we now have shots against COVID-19 hardly means it has disappeared. In fact, the coronavirus has already begun to resurface in other forms—or mutations—and will continue to do so until it’s completely stamped out. Vigilance has always been key, but it is all the more critical now.
SARS-CoV-2, the virus that causes COVID-19, is thought to have initially crossed into humans from animal reservoirs. That wasn’t a transaction that stopped once the pandemic reached humans a year ago: Since June, more than 200 human cases of COVID-19 have been traced to mink farms, indicating that the virus likely spread from humans to mink and then back again. In November, Denmark reported 12 cases of a unique strain of the virus with a cluster of variants that had not been seen before. Global concern about the outbreak prompted Danish Prime Minister Mette Frederiksen to order a cull of 17 million living mink and announce plans to end mink farming for the foreseeable future. In response, many countries—fearing that the outbreak could spread beyond Denmark—imposed stricter border controls with the country.
Despite that foresight, Canada announced this month that eight people at a mink farm in British Columbia had contracted COVID-19. The farm sent its animals and staff into quarantine and adopted enhanced biosecurity measures to protect against further infection—to little avail. Numerous U.S. states, including Oregon, have also reported outbreaks linked to mink farms. This raises serious concerns about the possibility of infections spreading outside farms—where they are at least contained—and becoming established in the wild.
If minks weren’t enough, attention has turned to a new strain of the virus that emerged in the United Kingdom, reported to be more transmissible than its counterparts. B.1.1.7., as the mutation is known, has prompted global chaos reminiscent of mid-March and led more than 50 countries to ban travel with the U.K. While B.1.1.7. is not reported to affect the severity of infection, it is much more transmissible than the standard variant of COVID-19—and has rapidly become the preeminent strain in southern England. A different strain—which shares a mutation with the U.K. strain—appears to have evolved separately in South Africa, where it has similarly become dominant.
These developments come at a critical time: in the midst of a winter surge in cases and mass distribution of vaccines against the standard variant of SARS-CoV-2. To understand the implications of the mink strain, and the recently detected new strains of the coronavirus within the U.K. and South Africa, for public health—and policy—we need to understand how viruses mutate, how these mutations spread, and what impact they can have.
SARS-CoV-2 is an RNA virus that has around 30,000 bases in its genetic sequence. Mutations—spontaneous changes that arise in the genetic sequence of the virus—are nothing out of the ordinary for RNA viruses. In fact, RNA viruses, such as influenza, mutate frequently during replication as the mechanism that copies the RNA is prone to errors. But mutations occur far less frequently in SARS-CoV-2, as its copying mechanism has a low error rate. That’s why the average case of SARS-CoV-2 contracted during the pandemic differs from the original Wuhan strain by only around 20 bases.
Still, thousands of mutations have been identified in SARS-CoV-2 viruses across the globe. Most are not a reason for concern: The vast majority of mutations are likely to be neutral, meaning they are neither advantageous nor disadvantageous for the virus. Disadvantageous mutations are good news for public health: They can disrupt the virus’s functions, such as the ability to bind and enter human cells, and impair its ability to spread efficiently between humans. Unfortunately, disadvantageous mutations usually get selected out, as they transmit less effectively.
The prospect of advantageous mutations, however, merits more concern. Advantageous mutations can help the virus bind to human cells more efficiently or escape an immune response altogether. In theory, advantageous mutations of a virus will be naturally selected over time, becoming the dominant strain in a community or population. Neutral mutations can also spread widely across populations, a fact that can make it difficult to discern whether a specific mutation is common due to random spread or because it is advantageous.
Mutations accumulate as the virus makes more copies of itself; in that sense, it’s only natural that we’ll see more mutations of the coronavirus over time. But when levels of viral transmission and replication are high, selection pressure can cause advantageous mutations to accumulate. Selection pressures can arise when a virus adapts to a new species, faces a new treatment or immune response, or is thwarted by a vaccine.
SARS-CoV-2 appears to adapt quickly to new animal reservoirs; in one study conducted in China, the virus mutated and rapidly adapted to mice, establishing a new animal reservoir. Notably, the mutation that allowed the coronavirus to adapt to mice is a key component of the new strains spreading across the U.K. and South Africa. This suggests that the viral adaptation of COVID-19—and the spread between species—can happen relatively easily.
Mutations matter because they affect whether we recognize the virus and how we ultimately deal with it. Sometimes, tests—and our immune systems—can’t recognize a mutated virus. Antigen tests based on one strain of virus may not be able to detect new virus lineages or antibodies, and immune systems that have encountered a given viral strain may not recognize a new strain—which can make reinfection more likely. Most important, this reality is cause for tempering the global vaccine euphoria: The emergence of mutations could reduce the protection offered by vaccines and antibody treatments, all of which have been based on the original strain of COVID-19. The immunity generated by vaccines usually produces a complex response to many components of the viral protein—making them generally resilient to a few mutations in the virus—but a strain with a large number of changes has the potential to escape immune responses directed against the original strain.
Most coronavirus vaccines work by generating an immune response to the spike protein, which is the part of the virus that binds to the ACE2 receptor on human cells. ACE2 is an enzyme found in many of our tissues that has many important functions, including regulating our blood pressure. At the same time, the prevalence of ACE2 receptors also provides ample opportunity for coronaviruses to enter our cells.
Since the binding of the virus with a receptor is a necessary step for infection, it was previously thought that mutations featuring changes in the spike protein would not lead to infection and, by consequence, spread. But scientists have recently discovered several mutations in the spike protein that don’t reduce the ability of the virus to bind to receptors, flipping conventional wisdom on its head. Overall, mutations in the spike protein have proved more resistant to neutralization by dominant-strain antibodies, raising concerns about their potential consequences—particularly as the standard variant of the coronavirus is greeted with a small squadron of highly effective vaccines.
All of this has immense real-world consequences. Just as the world is developing new coronavirus-related drugs, there are reports of people who’d been infected with an earlier strain of the virus becoming reinfected with a different variant. Thus, there is reason to be concerned that some mutations of the virus could escape immune responses generated by standard inoculation, such as the Pfizer-BioNTech or Moderna vaccine.
Whether that applies to the mink and U.K. variants is yet to be seen. Preliminary analyses suggest the mink mutation is less likely to be susceptible to antibodies directed against the standard strain of SARS-CoV-2. To be sure, these studies were conducted in laboratories—and thus do not capture the full range of human immune responses. But the possible implications for vaccine efficacy are worrying.
And though BioNTech CEO Ugur Sahin has assured the world of the high likelihood that his company’s vaccine offers immunity against B.1.1.7., one of the deletions in the U.K. strain is thought to be an adaptation able to escape immune responses directed at the original strain. Recently, an immunocompromised patient with COVID-19 developed a strain with the B.1.1.7. deletion during treatment with convalescent plasma, which contains antibodies from people who’ve recovered from the standard variant of the virus. The new mutation appears to have allowed the virus to escape these antibodies, allowing it to survive even after treatment.
The solution is the same as it has been all throughout the pandemic: adhere to public health guidelines that mitigate the spread of COVID-19, whatever its form. Since mutations occur through random processes and accumulate with uncontrolled spread of the virus as well as through adaptation to different selection pressures, mutations are less likely to threaten immune responses when transmission rates are lower, both among humans and other species.
We know what to do on the human front. But to prevent new reservoirs of virus from emerging in other species, governments must urgently reform farming practices, enhance biosecurity measures, and actively keep tabs on COVID-19 by frequently sequencing the virus in humans and animals. This data must be shared globally so outbreaks can be identified and controlled rapidly, before they spread across different regions.
The world has invested billions of dollars in coronavirus vaccine development. Now that safe and effective vaccines are becoming available, it’s essential we protect these precious resources. The best way to do this is to control virus transmission using the measures we know work—testing, tracing, isolating, mask-wearing, and physical distancing. Vaccination is, of course, also a very important part of this strategy, but must be rolled out alongside the tried and true methods. Controlling the pandemic globally requires us to work together. Only then can we be protected from the very real threat posed by virus mutations today—and in the future.