COVID’s Turbo-Mutation Is Killing This Vax Dream, So What’s Next?

·7 min read
Illustration by Elizabeth Brockway/The Daily Beast
Illustration by Elizabeth Brockway/The Daily Beast

Two months after scientists in South Africa alerted the world to the new, highly transmissible Omicron variant of the novel coronavirus, the global surge in infections resulting from the variant is finally subsiding.

To be clear, exhausted health-care workers in overcrowded hospitals are still fighting to save lives. But many epidemiologists are beginning to look ahead to a post-Omicron world.

The pandemic experts The Daily Beast spoke to were unanimous. Omicron is not the end. New variants–“lineages” is the scientific term–are coming. Worse, a host of entirely new coronaviruses lurk in animal populations and could make the leap to human beings at any time, seeding a whole new pandemic after or on top of COVID-19.

A new vaccine that works equally well against all lineages of SARS-CoV-2, as well as any future coronavirus, could blunt both. A “pan-coronavirus” vaccine is the holy grail of public health. Dozens of labs all over the world, including several in the U.S., are working overtime to develop one.

Why Omicron Is More Likely to Kill Americans

Scientists hope universal vaccines will hugely simplify global efforts to end the current pandemic and prevent the next one. Some insist it’s a better approach than trying to tailor vaccines for particular lineages. An Omicron-specific jab, for instance.

“We are going to have to come up with long-term vaccine solutions that don’t necessitate chasing the latest variant,” James Lawler, an infectious disease expert at the University of Nebraska Medical Center, told The Daily Beast.

A pan-COVID vaccine gets ahead of the pathogen. Lineage-specific vaccines chase after it. Barton Haynes, an immunologist with Duke University’s Human Vaccine Institute, called the latter approach “whack-a-mole.” “Wait until something happens, then do something about it.”

The solution, Haynes told The Daily Beast, is “greater uptake of the vaccines we have and good use in the future of the vaccines being developed in the second generation of COVID vaccines–i.e., pan-coronavirus vaccines.”

When the COVID-19 pandemic took hold in late 2019, the priority was developing a vaccine for COVID-19. In one of most impressive feats of pharmaceutical development in world history, in roughly a year the world had access to several highly effective vaccines, including two using new messenger-RNA technology.

But uneven vaccine distribution, and entrenched anti-vax minorities in countries with easy access to the jabs, gave SARS-CoV-2 room to evolve. The vaccines softened COVID’s impact until the new, more lethal Delta lineage evolved in mid-2021. Booster shots helped blunt Delta–and then, late last year, Omicron evolved.

Omicron with its dozens of mutations somewhat reduces the effectiveness of the vaccines, motivating some of the leading pharmas to develop new versions of their jabs that attack Omicron where it’s weakest—hopefully restoring the vaccines’ previous levels of effectiveness. Both Pfizer and Moderna expect their Omicron-specific vaccines to be ready in March.

But Omicron, which is highly transmissible but often less severe than Delta, surged fast and faded with equal speed. Cases peaked in the worst-hit countries over the past couple weeks and are now dropping fast. In the U.S., new infections peaked at around 800,000 a day last week before declining to 700,000 a day a few days later.

It’s increasingly likely that, by the time the Omicron-specific jabs are ready, Omicron won’t be the main problem any more. “I don’t think we’re going to get an Omicron vaccine in time to affect this initial Omicron wave,” Lawler said. And some new lineage will almost certainly take its place, Lawler added.

Meanwhile, totally different coronaviruses loom. They all have two things in common—the distinctive spike protein that helps them grab onto our cells, and a tendency to cause respiratory infections in people.

Scientists have named 46 coronaviruses so far. Most reside in animal populations; bats, pangolins, tropical cat-like animals called civets. Any one of these animal viruses could leap to the human species–and a bunch already have. Humanity has suffered through outbreaks of SARS-CoV-1, MERS and now SARS-CoV-2. “Why wouldn’t there be a SARS-CoV-3?” Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, told The Daily Beast.

Experts stress that ongoing deforestation and the growing trade in wildlife could mean increasing human exposure to coronaviruses in coming years and decades. Changchuan Yin, a University of Illinois at Chicago scientist, assessed–in a study that hasn’t yet been peer-reviewed–dozens of coronaviruses and identified several, including SZ3 in civets and the bat coronavirus HKU9-1, that seem to pose a high risk to the human population should they ever jump from their host species to us.

The increasing speed of SARS-CoV-2’s evolution–from the baseline virus to Delta to Omicron–undercuts the case for boutique jabs and underscores the rationale for pan-COVID shots. The growing threat from new coronaviruses only further makes that case.

A team of scientists at Duke, led by Haynes and his colleague Kevin Saunders, was one of the first to get to work on a universal vaccine, back in the spring of 2020. After months of work, they found an especially powerful antibody in a sample from someone who had recovered from a SARS-CoV-1 infection back in 2003.

That antibody, DH1047, targets the spike protein. Haynes, Saunders and their team immunized macaque monkeys and mice with DH1047, then exposed the animals to a menu of pathogens including SARS-CoV-2 and other coronaviruses.

“It worked wonderfully well,” Haynes said. One experiment produced a titer—a measure of antibody concentration—of 47,000. That’s six times higher than the typical titer resulting from one of the mRNA vaccines for COVID-19.

The National Institutes of Health has awarded the Duke team funding to begin manufacturing the antibody. Not only could it form the basis of a powerful, pan-COVID vaccine–it could also be the key ingredient in a new, post-infection therapy for COVID-19 and other coronavirus infections.

A team led by Kayvon Modjarrad at the Walter Reed Army Institute of Research in Maryland is working on its own universal vaccine–and has also shown promising results. Modjarrad’s team isolated a fragment of a coronavirus spike protein called a “spike-ferritin nanoparticle” and exposed it to monkeys then human subjects starting last spring.

The results, so far, are encouraging. “This vaccine stands out,” Modjarrad said in a statement. The spike-ferritin nanoparticle “may stimulate immunity in such a way as to translate into significantly broader protection.” The goal, Modjarrad explained, is “safe, effective and durable protection against multiple coronavirus strains and species.”

If there’s a downside, it’s that a pan-COVID vaccine might be slightly less effective than, say, the current mRNA vaccines were against the earliest SARS-CoV-2 lineages. The mRNA vaccines peaked at 90-percent or greater effectiveness, but have slowly lost effectiveness as newer lineages evolve to evade them.

The promise of a universal vaccine is that, while potentially less effective overall, it won’t lose effectiveness even as the various coronaviruses it combats mutate in an effort to thwart it.

A universal vaccine could also hugely simplify the logistics of immunizing large populations. You get one vaccine for a whole bunch of different viruses and lineages. You might eventually need a booster, sure–but if the jab works as advertised, you wouldn’t need to follow up with a different shot each time some new lineage pops up.

There’s still a lot of work to do to turn these promising antibodies and nanoparticles into robust vaccines, test them on large human populations and get them past government regulators.

The Next Big COVID Variant Could Be a Triple Whammy Nightmare

Haynes stressed his team is trying to get to large-scale human trials “as quickly as possible.” But in the worst-case scenario, it could take years to develop, test and deploy a pan-COVID vaccine, warned Yoshihiro Kawaoka, a virologist at the University of Wisconsin-Madison who is working on his own universal jab.

But we’re already in year three of the SARS-CoV-2 pandemic and there’s no end in sight. We’re going to be living with this virus, and possibly other coronaviruses, for a while. It’s time to think long-term about vaccines that can get ahead of the viruses.

Read more at The Daily Beast.

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