What are Quotes from Experts?
January 19-21, 2021
What new variants of SARS-CoV-2 are concerning?
“We have heard increasingly in recent weeks about new variants (or strains) of SARS-CoV-2 detected in different parts of the world that are causing concern among scientists. These new strains appear to have become more transmissible (contagious) than previous strains. Some of the new strains may also diminish the ability of antibodies from previous infection or vaccination to recognize the virus. The greater transmissibility of these viruses means that they will likely be harder to control than previous strains. Currently we are focused on 3 main variants of concern, but it is important to note that we expect the virus to continue to evolve as it infects more people worldwide, so additional variants are likely to emerge. That means that we must not focus only on the concerning variants that have already been identified — we must also be alert to the possible emergence of more new variants.” (Posted January 21, 2021)
“As viral sequencing ramps up, more variants will be detected. Currently, three variants appear to be of concern: B.1.1.7, B.1.351, and P.1, first detected in the UK, South Africa, and Brazil, respectively. B.1.1.7 has an unusually large number of mutations, including many in the spike protein. Although this is the best established for B.1.1.7, all of these variants may transmit better from person to person.” (Posted January 19, 2021)
“There are two main concerns about new SARS-CoV-2 mutations: First, these mutations persist because they enable efficient viral transmission, either by changing the part of the respiratory tract the virus infects, or by infecting human airway cells more efficiently; Second, new mutations could accumulate to allow the virus to evade our immunity, whether generated by vaccination or natural infection.
“Both of these scenarios are likely to involve substitutions of amino acids in the spike protein, which binds to receptors on our cells and allows the virus to enter and replicate. This is why strains like the UK variant B.1.1.7, and a South African variant, which have been associated with greater rates of spread since they appeared last year, are particularly concerning: the UK variant includes 8 different amino acid changes in the spike protein, several of which cluster near the part that binds to the human cell ACE2 receptors so the virus can invade.
“This same part of the spike protein is also a main target of antibodies that play major roles in protecting us from disease and possibly even preventing infection. Thus, there is also concern that the accumulation of these types of spike changes may allow a new variant to escape immunity generated in response to infection with earlier virus strains, as well as to immunity generated from the spike protein that is incorporated into vaccines, which was designed with the first SARS-CoV-2 sequences nearly a year ago.” (Posted January 19, 2021)
How do mutations in these variants change the virus’s ability to infect people?
“The scientific community is still studying the mechanisms by which specific mutations alter the virus’s ability to infect people. Most work is focused on changes to the amino acids that make up the viral Spike (S) protein, which is responsible for attaching the virus to cells so that it can enter and infect them. It seems likely that some changes to the structure of Spike could allow it to attach more efficiently to human cells, which could lead to greater transmissibility. Some mutations may also change the structure of the Spike protein in a way that makes it more difficult for antibodies to attach to it. This would help ‘hide’ the virus from the immune response. It is less clear whether mutations in the current variants of concern specifically alter antibody recognition to a meaningful degree.” (Posted January 21, 2021)
“Current evidence suggests that mutations in B.1.1.7 allow increased viral replication—and larger viral loads—in the upper respiratory tract of infected persons. This likely accounts for the increased transmissibility, at least in part.” (Posted January 19, 2021)
“So far, one mutation, D614G, that occurred early last year quickly became the predominant strain worldwide. It allows the virus to replicate more efficiently in the upper airway to enhance shedding and the efficiency of transmission. Fortunately, this substitution does not render the virus resistant to the antibodies generated in vaccinated persons. Likewise, another substitution in the spike, N501Y, which is shared by both the UK and S. African variants, does not allow the virus to escape neutralizing antibodies produced in response to vaccination.” (Posted January 19, 2021)
Why might several different variants of SARS-CoV-2 have appeared recently?
“I think most people studying viral evolution agree that the appearance of these variants now mostly reflects the very large number of cumulative infections that have occurred worldwide since the start of the pandemic. On average, one mutation may occur every time or every other time the virus infects a new person. Each mutation is kind of like pulling a slot machine — the chance of hitting the jackpot on any individual pull is small, but you pull millions of handles simultaneously the chances are dramatically increased. Viruses that ‘hit the jackpot’ by accumulating a set of mutations that makes them more transmissible will then increase in the population due to natural selection. As more people become immune through prior infection or vaccination, while transmission rates remain high, we may expect this sort of adaptation to continue.” (Posted January 21, 2021)
“The essentially unfettered spread of SARS-CoV-2 in populations without immunity worldwide has set the stage for large numbers of viral replication cycles, each associated with random mutations in the viral genome. However, natural selection processes, both within infected people and during transmission, are also occurring and can allow certain variants to predominate.
“Variants like B.1.1.7 may be able to ‘take over’ because they produce many more infectious particles that can spread from person to person than other variants. Some of the mutations that have arisen, especially in the spike protein, also appear to alter the antigenic profile of this protein—essentially the way the protein looks to the immune system—and may have been selected for improved viral replication in the face of the human immune response. It is important to note, however, that none of the variants studied to date can fully escape the immune responses generated in people in response to natural infection or vaccination. On the other hand, monoclonal antibody therapies are more likely to suffer large losses in efficacy due to changes in the spike protein.” (Posted January 19, 2021)
“SARS-CoV-2, like other RNA viruses, is constantly generating mutations as it replicates inside infected people. The reason that SARS-CoV-2 has been accumulating many more mutations during the past several months is probably related to increasing spread and transmission around the world. The more viral replication occurring in the human population, the more random mutations are generated, and the greater the chance that one of these mutations will improve infection or transmission, resulting in a new viral variant that outcompetes earlier ones. Genetic crossover between two different virus strains that infect the same cell can also generate rapid changes.
“Human immunity, either from vaccination or infection, can also create conditions enabling new mutant variants to outcompete current variants; however, there are probably not enough immune persons yet to allow this kind of selection to occur. As herd immunity grows during the coming months with continued infections and increasing vaccination, we may see this kind of selection increase to the point where new strains that resist that existing immunity could be selected and replace earlier strains. This is the situation we see with influenza virus, where our immunity from past infections selects for rapid changes in the proteins targeted by the vaccine. This is why we need to be vaccinated annually with influenza virus strains predicted to be the most common during the coming transmission season.” (Posted January 19, 2021)
If new—or future—variants of SARS-CoV-2 evade currently approved vaccines, are there vaccines in development that might prove more effective or that target a different part of the virus?
“A good thing about current vaccines is that they can be updated pretty quickly. So, if the virus evolves to evade vaccine-induced immunity, then I think we can definitely envision a situation like we have for influenza vaccines, in which the SARS-CoV-2 vaccine is periodically updated to keep pace with viral evolution. We do not yet know whether this will become necessary, but I think we are positioned to adapt quickly if it does.” (Posted January 21, 2021)
“All vaccines that have been deployed to date or are currently in development utilize the SARS-CoV-2 spike protein as the target of the human immune response. In the short to medium term, modification of the spike protein sequence in the vaccine to account for genetic changes in the virus should re-establish vaccine efficacy if it becomes significantly degraded.
“These changes are easier to make for certain types of vaccine platforms, like the mRNA-based vaccines (Pfizer and Moderna), and more challenging for others, like the virus-vectored vaccines (AstraZeneca and Johnson & Johnson). Eventually, it would be desirable to develop vaccines that target regions of the SARS-CoV-2 spike where mutations would prevent the virus from functioning, such as the S2 region. Influenza A virus vaccines provide a useful analogy. Existing vaccines largely target portions of the influenza virus spikes that can mutate while the virus is still able to infect people, which is why the vaccine must be fine-tuned every flu season. Current efforts are aimed at targeting more genetically constrained parts of the flu spike protein—that is, parts that are so essential that any mutation would effectively disable the virus—to make ‘universal’ flu vaccines. In the medium term, it is probable that a strategy similar to the one currently used for flu will be necessary to protect the global population against SARS-CoV-2.” (Posted January 19, 2021)
“Fortunately, the vaccines that have been approved are types—mRNA vaccines or adenovirus-based vaccines—where the new, resistant SARS-CoV-2 spike protein gene sequence could be quickly swapped, and a new vaccine could be tested minimally and manufactured within a few months (unlike flu vaccines, which take much longer to prepare each year). It is also possible that other types of vaccines, such as live-attenuated (weakened virus) versions that include the full complement of the SARS-CoV-2 proteins and therefore more targets of immunity, could yield more durable immunity that is also less susceptible to new variants developing resistance. However, live-attenuated vaccines require much more thorough safety testing than the mRNA and adenovirus-vectored vaccines, which is why these were the first to be deployed, so they are still probably years away from potential licensure.” (Posted January 19, 2021)
Kartik Chandran, PhD, Professor of Microbiology and Immunology, Albert Einstein College of Medicine
Thomas Friedrich, PhD, Professor, Department of Pathobiological Sciences, University of Wisconsin School of Veterinary Medicine
Scott C. Weaver, PhD, Professor and Chair, Department of Microbiology and Immunology, Director, Institute for Human Infections and Immunity, Scientific Director, Galveston National Laboratory, University of Texas Medical Branch
I have nothing to disclose.
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