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SARS-CoV-2 is evolving to avoid immune responses

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  • SARS-CoV-2 is evolving to avoid immune responses

    Over the summer, you could almost hear a sigh of relief rising from the portion of the research community that was tracking the evolution of the SARS-CoV-2 virus. Viruses, especially those new to their hosts, often pick up mutations that help them adapt to their new habitat, or they evade drugs or immune attacks. But SARS-CoV-2 seemed to be picking up mutations at a relatively sedate pace, in part because its virus-copying enzymes had a feature that lets them correct some errors.

    But suddenly, new variants appear to be everywhere, and a number of them appear to increase the threat posed by the virus. A new study helps explain the apparent difference: while new base changes in the virus's genetic material remain rare, some deletions of several bases appear to have evolved multiple times, indicating that evolution was selecting for them. The research team behind this new work found evidence that these changes alter how the immune system can respond to the virus.

    This looks familiar

    The researchers' interest in deletions started with their involvement with an immunocompromised cancer patient, who held off the infection for over two months without being able to clear the virus. Samples obtained from late in the infection revealed two different virus strains that each had a deletion in the gene encoding the spike protein that SARS-CoV-2 uses to attach to and enter cells.

    When the researchers searched a database of other viral genomes, they found six other cases where the same or similar deletions seem to have evolved in other patients. This caused them to go back and look at a collection of nearly 150,000 viral genomes. They found that over 1,100 of them carried deletions in the spike protein. But critically, they found that these weren't distributed randomly. Ninety percent of the deletions clustered into four distinct areas of the spike gene.

    That could be for one of two reasons. It's possible that these viruses are related by common descent and all inherited the same ancestral deletion. Or these deletions could be useful from an evolution perspective, and so whenever they happen to occur, they end up being kept around.

    To figure out what's going on, the researchers built an evolutionary tree of the viruses using mutations that occurred outside the spike protein. This showed that, outside of the deletions, the viruses were often distantly related. This indicates the latter option is likely to be true: the deletions often occurred independently and were just kept around at an unusually high rate. One specific deletion seems to have occurred at least 13 different times, and some of the deletions have been around since early in the pandemic.


    If these deletions are being kept around, then the obvious question is "Why?" To find out, the researchers figured out how each of the deletions would alter the spike protein produced by the mutant form of the gene. They then compared this information to what we know about the structure and function of the spike protein. None of the regions turned out to be essential for the spike protein to do its job (which you'd expect, given that deleting those would probably inactivate it). Instead, some of the sites had already been identified as locations where antibodies to the spike protein would stick to it.

    So, the researchers produced these deletion versions of the spike protein and tested whether an antibody that can neutralize the virus can stick to them. For one antibody, the answer was "yes": two of the deletions completely blocked its ability to stick to spike, while the other two had no effect.

    That's bad news. But the immune response typically involves a collection of different antibodies that can stick to a virus. And, when the researchers tested patients' plasma (which should have a mix of antibodies) against the mutant forms, some of the antibodies present were still able to stick to it. So, while any of these deletions seems to be capable of limiting the immune system's ability to neutralize the virus, the deletions don't eliminate that ability entirely.

    And, while these mutations are worrying, they're not yet a clear threat.

    Some of these deletions have already been seen in strains that seem to have increased spread in recent months. And, while the research team was doing all these experiments, reports came out of four additional strains that were spreading quickly and carried deletions in spike.

    Again, so far, there's no indication that any of these strains can evade the immunity built up by earlier infection or one of the vaccines currently in use. But the results make clear that the virus is evolving in response to the immune system's reaction to it, and we can't guarantee that further changes won't make COVID-19 harder for our immune systems to keep at bay.

  • #2
    For those that don't understand. It's basically just saying that covid does what viruses tend to do. It's evolving to survive just like other living organisms. It's for this reason that the flu shot changes each year. So don't panic. This isn't unexpected.

    The Flu isn't any more deadly than it was 100 years ago. It's simply that it has evolved to survive. Its goal is not to kill you. Simply to not die itself.


    • #3
      Good news.


      Tweaking COVID vaccines to fight variants won’t require big trials, FDA says

      The regulatory agency is drawing on its experience with annually tweaked flu shots.

      With concerning coronavirus variants erupting around the world, the US Food and Drug Administration is ironing out how to rapidly review vaccine tweaks that better protect against the mutants—and the regulatory agency is turning to its experience with annual flu shots to do so.

      In a statement late Thursday, the regulatory agency said it is actively hashing out what kind of “streamlined” clinical data makers of authorized COVID-19 vaccines could submit. The agency expects to have a draft of its guidance in the next few weeks.

      The announcement suggests that makers of authorized vaccines will not be required to submit reams of data from large, months-long clinical trials, as they did for their initial authorizations. Still, data on any altered vaccine—however pared down—would still have to be enough to convince FDA scientists that a next-generation shot is safe and effective against variants. Vaccine alterations may include changes to the initial vaccine design or additions of new vaccine components, the FDA said.

      So far, the FDA has issued emergency use authorizations for two COVID-19 vaccines, an mRNA-based vaccine made by Moderna and another by partners Pfizer and BioNTech. (The FDA is now reviewing an EUA application for a third candidate, made by Johnson & Johnson, which is a non-replicating adenovirus-based vaccine.) Both mRNA vaccines showed around 95 percent efficacy in massive international Phase III trials. However, those trials were conducted prior to the rise of concerning variants, some of which appear to be able to evade immune responses. Early clinical data does indeed suggest that vaccine efficacy will be reduced by the currently emerging variants—though not eliminated entirely.

      The FDA emphasized this last point, writing, “To be clear, while we continue to develop an understanding of and address any impact of variants on FDA-regulated products, at this time, available information suggests that the authorized vaccines remain effective in protecting the American public against currently circulating strains of COVID-19.”

      “We must prepare”

      But it’s also clear that the pandemic coronavirus, SARS-CoV-2, is continuing to evolve, becoming more transmissible and able to evade immune responses. We’re likely to continue to see concerning variants arise. "We must prepare for all eventualities," FDA's acting Commissioner Janet Woodcock, said on a call with reporters.

      To prepare and develop its new guidance, the agency is drawing on its experience with annual flu shots. “Influenza vaccines and diagnostics are often modified each year to address the predicted predominant strains circulating globally. The agency has created and used regulatory processes that facilitate these updates,” the agency wrote. “We will utilize our experience with influenza to help inform a path forward if SARS-CoV-2 variants emerge against which currently authorized vaccines are not sufficiently effective.”

      Moderna, Pfizer, and BioNTech have all said they are looking into tweaking their current vaccines to better protect against emerging variants. Their mRNA-based vaccine designs make this a relatively easy process. The vaccine works by delivering to human cells the genetic blueprint for a key SARS-CoV-2 protein—the spike protein. From there, the cells translate the code into protein, which then trains the immune system to detect and neutralize the virus.

      The variants seen so far have critical mutations in their spike proteins, so updating the vaccines is mostly a matter of making small changes to the blueprint delivered to cells. BioNTech’s CEO has previously said that the company could carry out such tweaking in just six weeks.

      Similarly, GlaxoSmithKline announced this week that it has partnered with German biotech firm CureVac to help bring its mRNA-based vaccine to market—and begin work on the next-generations of the vaccine to protect against variants. GSK and CureVac said they are working on developing a “multivalent” mRNA-based vaccine that could potentially protect against multiple variants at the same time.