Vaccine developers can't keep up with COVID's mutations

The FDA is allowing additional bivalent shots — but a new study suggests they don't work as well as they used to

By Troy Farah

Science & Health Editor

Published May 2, 2023 12:00PM (EDT)

Malik Jaffer, lead nurse, prepares a syringe with a Covid-19 vaccine, at the Peoples Congregational United Church of Christ, the site of the Ward 4 DC Covid Center, in Washington, D.C. on March 31, 2023. (Eric Lee for The Washington Post via Getty Images)
Malik Jaffer, lead nurse, prepares a syringe with a Covid-19 vaccine, at the Peoples Congregational United Church of Christ, the site of the Ward 4 DC Covid Center, in Washington, D.C. on March 31, 2023. (Eric Lee for The Washington Post via Getty Images)

In April, the U.S. Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) both updated their recommendations for COVID vaccines, providing more flexibility for higher-risk individuals who want additional protection from the SARS-CoV-2 virus that causes COVID-19. Most crucially, people who are immunocompromised or over the age of 65 are now allowed to get a second bivalent booster shot. For everyone else, the FDA and CDC have deemed them unnecessary at this time.

"This allows more flexibility for healthcare providers to administer additional doses to immunocompromised patients as needed," the CDC said in a statement.

It's important to note that COVID vaccines still do their job: overall, they protect against severe illness and death. What they don't do as well anymore is prevent infection.

This is encouraging news, but the question remains: Will anyone actually get the extra shot? While the first generation of COVID vaccines were warmly received by most people, the bivalent boosters have been far less popular. That's not entirely attributable to lack of public awareness: researchers say that vaccines haven't kept up with COVID's mutations, and the goalpost has shifted as to what we can actually expect vaccines to do.

There's a good reason why uptake was so strong for the first COVID vaccines. They worked extremely well at preventing hospitalization and death. Now that it's been a few years since they were made available to the public, a good amount of research demonstrates that they saved many lives, even in spite of inequity in the pandemic.

Which is a why it's a little strange that less than 17 percent of Americans have gotten the updated bivalent vaccine. That percentage represents a mere 55.7 million people, according to CDC data. In contrast, 69.4 percent of people, more than 230 million Americans, got the first COVID vaccine. Looking closer at the data, people over the age of 65 are far more likely to have gotten the updated booster: nearly 43 percent, or 23.3 million people. It remains unclear if many people will get a second bivalent booster, but at least the population who actually seems to want it has it available.

The bivalent vaccines were first issued last October and are slightly different from the original mRNA vaccines that were first released in late 2020. The first line of vaccines, which were licensed and developed by the biotech corporations Moderna and BioNTech and Pfizer, were designed to generate the spike protein that encircles the SARS-CoV-2 virus. Because this artificial spike protein that the mRNA vaccine generates is not attached to a virus, it cannot infect cells, but it can train our immune systems to fight when it encounters a real COVID virus.

The FDA and the CDC no longer recommend the older class of these vaccines, and instead have only authorized use of the updated bivalent versions — so-called because they contain two different mRNA-based spike proteins: one is the original vaccine, which mimics the first strain of SARS-CoV-2 that was circulating in 2019 and 2020. The second spike protein is more closely related to two different strains, BA.4 and BA.5, which are children of the omicron variant. Omicron first hit our radar in November 2021 and caused one of the biggest surges of infections in the pandemic thus far.

While infections from BA.4 and BA.5 made up the majority of cases for most of 2022, the landscape of COVID strains has changed dramatically. First there was something of a "variant soup" through most of the fall and winter, with a recombinant variant nicknamed Kraken (XBB.1.5) that has been responsible for most cases in 2023.

All these jumbled up letters and numbers represent specific changes in the virus DNA that can give it advantages against some (but not all) of our immune defenses. Monoclonal antibodies, for example, no longer work against Kraken, but Paxlovid does. Because none of the variants that are currently spreading are reflective of the vaccines, it begs the question: will they even work?


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A study published April 25 on the preprint server MedRxiv by a group of Austrian virologists analyzed blood samples and found that the newer vaccines do work against most strains of the virus — though they provided only only modest protection against BA.5, and did extremely poorly against XBB.1.5. Even people with acquired immunity from Kraken were unable to mount an effective immune response. The study did use a small sample size and has not been peer-reviewed, meaning outside researchers haven't studied this data, but it's still pretty alarming given that other data has pointed in this direction.

Another MedRxiv preprint, this one done by doctors at the Cleveland Clinic, reported "Effectiveness was not demonstrated when the XBB lineages were dominant." In fact, among more than 4,400 healthcare employees who were infected with COVID, vaccines were only 4 percent effective against infectious XBB variants.

It's important to note that COVID vaccines still do their job: overall, they protect against severe illness and death. What they don't do is prevent infection, as these recent studies suggest. In this study, the immunized still got sick, but they didn't die or go to the hospital. However, none of the people in the sample were immunocompromised and few were elderly.

The bivalent vaccines may not stand up very well against these new strains, which are evolving so fast that some experts even argue that we should rename the virus SARS-CoV-3 to emphasize its distant genetic drift from the original pathogen.

"Regardless of this one study, the evidence is mounting that we are utterly failing in our race against the virus' mutation," Blake Murdoch, a legal scholar and bioethicist at the University of Alberta Health Law Institute, wrote on Twitter. "And we have to pray that immune experience will play a massive role in saving people while we work on second generation scientific solutions."

Yet another study, this one published in the peer-reviewed journal Clinical Infectious Diseases on April 10, reported data from a randomized clinical trial; ominously, the study authors emphasized an "ongoing concern that the breadth of antibody response from current updated vaccines is not optimal for the pace of virus evolution."

According to the most recent stats from the CDC, Kraken infections made up an estimated 68.8 percent of cases during the week ending April 29. It is slowly but steadily being replaced by its offspring, strains like Arcturus (XBB.1.16) which made up 11.7 percent of cases and Hyperion (XBB.1.9) at 9 percent.

In other words, the bivalent vaccines may not stand up very well against these new strains, which are evolving so fast (as viruses normally do) that some experts even argue that we should rename the virus SARS-CoV-3 to emphasize its distant genetic drift from the original pathogen.

Dr. Monica Gandhi, an infectious disease doctor and professor of medicine at the University of California, San Francisco, told Salon in an email that these new omicron subvariants are increasing in prevalence because of increased transmissibility, evasion of antibodies or both.

"Even if subvariants have more mutations in their spike protein and are more adept at evading antibodies, as demonstrated for XBB.1.16, our immune system is fortunately 'redundant' and doesn't just rely on antibodies to protect us from infection," Gandhi said. "At this point, although XBB.1.16 does seem to evade antibodies from the bivalent vaccine per the data, we should feel comfortable that the bivalent vaccine is likely to stimulate our B cell response and protect the elderly [and] immuncompromised from severe disease."

But while the bivalent vaccines may be unlikely to prevent infection against the currently circulating strains in North America, it's worth repeating that they will still stop severe illness and death. For someone elderly or immunocompromised, even a small amount of protection can make a big difference.

Instead, what this growing body of data underscores is that we're not keeping up with the mutations the virus is developing, which could spell bigger problems down the road. As former White House COVID response coordinator Dr. Deborah Birx warned in an interview with Fortune last month, SARS-CoV-2 will keep evolving and could make other treatments useless as well.

"If we lose Paxlovid, we could easily double the number of deaths," Birx said. "I've been really upset that the federal government has not prioritized next-generation vaccines that are more durable, next-generation monoclonals, and long-acting monoclonals."

While we're currently dealing with the XBB lineage, that could easily change, especially since the virus is now endemic. It could spread from animals to humans again, or a newly evolved version of SARS-CoV-2 could start wreaking havoc. As the federal public health emergency sunsets on May 11, it's clear that we need to do more than put outdated vaccines into arms or we could be buried by yet another COVID surge.

"Trying to paint COVID as endemic flu will have serious consequences in the long run. We will feel workforce issues soon and long COVID might hurt our healthcare system country-wide. That could really be the next big impact of the pandemic," Dr. Rajendram Rajnarayanan, an assistant dean of research and associate professor at the New York Institute of Technology campus in Jonesboro, Arkansas, told Salon in an email. "We don't have to feel pressured to move on from a real public health threat. We have a collective responsibility to protect our seniors and immunocompromised. Letting the virus spread unchecked is never a viable option."


By Troy Farah

Troy Farah is Salon's science and health editor specializing in drug policy and pandemics.

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