Viruses reproduce by taking over the replication machinery of host cells to make copies of their own genetic material, or genome. Unlike cellular organisms, whose genomes are made of DNA, viruses can encode their genomes as either DNA or RNA. Coronaviruses like SARS-CoV-2—the virus responsible for COVID-19—use RNA to store their genetic information, and copying RNA is more prone to mistakes than copying DNA. Researchers have shown that when a coronavirus replicates, around 3 percent of its copies contain a new random error, also known as a mutation.
A virus that is widely circulating in a population and causing many infections has more opportunities to replicate and thus to mutate. Most mutations are inconsequential glitches that do not affect how the virus works in a significant way. Others may even be detrimental to the virus. But a small fraction of the errors will prove advantageous to the virus, for example making it more infectious.
As a virus mutates through the replication process, the resulting mutated version of the virus is called a variant. Public health agencies may give special labels to groups of variants that share a characteristic or attribute. These groups may contain variants that come from a single lineage, like an inherited trait in a family tree, or those that arise independently but behave similarly. In the case of SARS-CoV-2, variants are classified and labeled using letters of the Greek alphabet, e.g., the Delta and Omicron variants.
While it’s not possible to stop SARS-CoV-2 from mutating, health experts say it is possible to reduce the chances that a new and more deadly mutation will arise by limiting the virus’s spread. This is why public health interventions like wearing masks, physical distancing, and vaccinations are important: they reduce the total number of times the virus can replicate and therefore the chances that it can develop a more dangerous mutation.
Over the course of the pandemic, numerous SARS-CoV-2 variants have arisen in the United Kingdom, Brazil, California, South Africa, and other areas. The Delta variant, which originated in India in late 2020 and within a few months had spread to more than 60 countries, is currently the predominant variant of the virus in the United States. The Delta variant is about two times more infectious when compared to other variants, and early data suggests it can cause more severe illness in unvaccinated people than previous variants.
The proliferation of variants has prompted concerns that they might make existing vaccines less effective. Because COVID-19 vaccines target a specific area of SARS-CoV-2 called the spike protein, mutations to the spike protein gene may lead to viruses that can cause illness even among those who have been vaccinated (commonly called a breakthrough infection).
But the COVID-19 vaccines currently in development or those that have been approved work by eliciting a broad immune response and so are expected to provide at least some protection against new virus variants. Indeed, early research suggests vaccines developed by Pfizer-BioNTech, Moderna, and Johnson & Johnson are all highly effective against preventing severe disease caused by the Delta variant.
Variants are classified into different categories by the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC):
- A variant of interest is a SARS-CoV-2 variant that, compared to earlier forms of the virus, has mutations that are predicted to lead to greater transmissibility, evasion of the immune system or diagnostic testing, or more severe disease.
- A variant of concern has been observed to be more infectious and more likely to cause breakthrough infections. The Delta variant falls under this category.
- A variant of high consequence is one for which current vaccines do not offer protection. No SARS-CoV-2 variants currently fall under this category.
mRNA vaccine technology, used in the Pfizer-BioNTech and Moderna vaccines, allows companies to create a new vaccine, or booster, more quickly than with viral-vector or protein-based methods. Drug companies have begun adjusting the vaccines to target known variants and are testing these adjustments in animals. The clinical trial process for adjusted vaccines is shorter than the trial process used to obtain emergency-use authorization.
Since most coronaviruses have regions of their spike proteins in common, some scientists are exploring the possibility of developing a “pancoronavirus” vaccine to target those shared regions and provide protection against variants and other types of coronaviruses.
Research groups, including the Bjorkman lab at Caltech, are designing such vaccines. The challenge they face: When a vaccine stimulates the immune system, it tends to produce antibodies that target the receptor-binding domain (RBD), the region at the tip of the protein spike where the protein binds to the host cell. But that region is not necessarily the same across different coronaviruses. Nonetheless, it might be possible to create a vaccine against one sub-grouping of coronaviruses—SARS-like betacoronaviruses—by targeting a portion of the RBD that is less variable. It seems likely, though, that a pancoronavirus vaccine would need to trigger immune responses that target non-RBD regions of the spike protein.