The Register Citizen (Torrington, CT)
Tweaking virus vaccine for variants
Yale doctor: Scientists can replace portion of drug to adapt to mutations
“The concern now is, obviously, if we keep getting more variants that it may be worse.” Dr. Onyema Ogbuagu, Yale Center for Clinical Investigation
Scientists and the world’s population are in a race against the coronavirus, to get as many people vaccinated as quickly as possible and to stay ahead of the mutations that are growing more common.
The “beauty” of the Pfizer-BioNTech and Moderna vaccines, according to Dr. Onyema Ogbuagu, who led the Pfizer trial at the Yale Center for Clinical Investigation, is that they can be tweaked to target new variants as they arise. It’s just a matter of replacing one bit of protein with another, he said.
The technology used to create both vaccines, known as messenger RNA (mRNA), is highly effective in protecting against COVID-19, and also easily can be altered to fight variant viruses, he said.
Ogbuagu, one of the first five people to be vaccinated at Yale New Haven Hospital on Dec. 15, 2020, said the original vaccine appears to be effective against the “U.K. variant,” technically known as B.1.1.7. That variant, which has spread to 28 states, including eight cases so far in Connecticut, may become the dominant coronavirus strain in the U.S. by March, the state Department of Public Health has said.
“The Pfizer vaccine worked against that,” Ogbuagu said. “There’s a more concerning variant … the South African variant, that has multiple variations in the spike protein.” That spike is what attaches to cells and infects them, and it is what the vaccines target. The South African variant was found in the U.S. for the first time Thursday, in South Carolina.
The Moderna vaccine has shown “a sixfold reduction … of neutralizing capacity” against the South African variant, Ogbuagu said. “The virus was a little more able to evade the immune response. The concern now is, obviously, if we keep getting more variants that it may be worse.”
“It’s almost like a race between trying to get people vaccinated or we’ll be eaten up by the virus,” Ogbuagu said. “You’ll see where the balance tilts in the upcoming weeks to months.”
The genetic material of the coronavirus, SARSCoV-2, is RNA, similar to what makes up viruses that cause flu, the common cold, hepatitis C and Ebola.
“We expect RNA viruses to mutate. It’s part and parcel of being an RNA virus,” said Dean Sten Vermund of the Yale School of
“Part of the tragedy of not having done a much better job shutting down viral transmission in 2020 because, by being sloppy about it, it kind of invites variants to emerge.” Dean Sten Vermund
Public Health. “Having a different virus for influenza every year is not a surprise.”
Facing viral mutations now, as vaccinations are just getting started, is “part of the tragedy of not having done a much better job shutting down viral transmission in 2020 because, by being sloppy about it, it kind of invites variants to emerge,” Vermund said.
The two new vaccines use mRNA to signal the immune system to attack the virus, making it simple to create new vaccines for new variants. “That’s what’s being done already by Moderna and Pfizer. They’re both working on booster shots,” Ogbuagu said.
As more variants emerge
— two others are from Brazil and California — it may be that previous versions of the vaccine won’t protect against them, requiring boosters, Ogbuagu said. “We’re going to be chasing our tail somewhat until we’re able to vaccinate enough people to develop this so-called herd immunity and snuff out the virus in the U.S.”
As more variants emerge, vaccines may be made up of multiple versions in one vial, Vermund said, just as the quadrivalent flu vaccine is designed to protect against four influenza strains.
When the virus mutates, “if you then create another vaccine that is a better fit, it mimics the new structure of the variant coronavirus spike protein,” Vermund said. “Then you can make what we call a polyvalent
vaccine. And we’ve got lots of polyvalent vaccines — for example, human papillomavirus, we started out with quadrivalent, four types, and now it’s nonavalent, nine types.
“The tough challenge was making the first mRNA vaccine,” he said. “Now that they’ve made it, it’s relatively straightforward to make the second and third and fourth.”
The familiar spikes on the coronavirus, a protein, are “important because that’s how the virus attaches to the cells in the body,” Ogbuagu said. The way to prevent infection “is to block the key from the lock,” he said.
The mRNA in the vaccines tells the body’s cells to make the same protein that is in the coronavirus’ spike. This activates the immune system, which creates antibodies against the protein, Ogbuagu said. “It’s kind of a reverse engineering,” he said.
When the virus mutates, the genetic code in its spike changes. “You can then make an mRNA template that codes for … any protein,” including the one from the mutated virus, Ogbuagu said. “The point is that mRNA encodes for whatever you want it to do. … When the virus comes in looking the same way, you already have preformed antibodies to block it.”
The U.K. variant is “50 percent to 70 percent more transmissible” than the first version of the coronavirus, said Dr. Richard Martinello, medical director for infection prevention at Yale New Haven Health. “What that allows that variant to do is really take off in a population.” It also may be more lethal, although that finding is preliminary, according to the Centers for Disease Control and Prevention.
While the coronavirus doesn’t appear to mutate as quickly as influenza, at least so far, it also doesn’t seem to be as restricted to one part of the year, the way flu, the common cold and a host of other respiratory diseases tend to hit hardest in winter.
While those diseases are most common during the cold, dry months and, with the coronavirus, “the cases we have during the winter have been higher than ever … it’s more likely than not that it’s not showing seasonality,” Ogbuagu said.
“The challenge is not necessarily getting the vaccine every year but will the vaccines that we have work against the virus if it continues to change,” he said.
Both Ogbuagu and Vermund said vaccinating as many people as quickly as possible is the ultimate goal. “It’s in everybody’s selfinterest to control the virus everywhere,” Vermund said. “Every single new infection presents the possibility of the virus mutating into a new variant.”
“The worst-case scenario is that coronavirus becomes like flu or worse and we’re continuously having to develop new vaccines and continuously having to adjust the cocktail and continuously having to coax and cajole enough people to get the vaccine.
“We’ve been urging all Americans to get flu vaccine for years, and we don’t get a high enough proportion vaccinated to drive down incidents adequately to drive down death and also mutations,” Vermund said. “So it would be great if we could do much better with coronavirus.”