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COVID-19 vaccines work incredibly well to prevent serious disease, but future boosters will likely need to be tailored to target new and existing variants, boost immunity, and ultimately help regain control of the pandemic.
The vaccines currently in use were designed to target the original strain of the virus, which is radically different from the highly transmissible variant of Omicron that became globally dominant within weeks of its identification.
Protection against infection was significantly reduced with Omicron, largely due to dozens of mutations on the virus’ spike protein, making it much easier to spread through vaccinated and unvaccinated populations than with the variants. previous ones.
But while the defense against hospitalization has held up remarkably well against this new challenger, immunologists and virologists agree that updating vaccines to be more similar to circulating variants will provide better long-term protection. .
“Omicron is different enough that I think we need to update it,” said Deepta Bhattacharya, immunologist and professor at the University of Arizona.
“In a way, I guess I’m a bit surprised that the third doses did as well as they did.”
Vaccines resist well to Omicron
New research shows how boosters resist the Omicron wave – still protecting against infection, symptoms and most importantly hospitalization. But how long this protection lasts is still an open question.
A new report from the US Centers for Disease Control and Prevention found that while vaccine effectiveness against Omicron hospitalization fell to just 57% in people who were more than six months away from a second vaccine, it rose to 90% with a booster.
A second CDC report looked at 25 US states between April and December and also found that while defense against infection declined, those with boosters had significantly higher protection against symptoms both when Delta was dominant and when Omicron was the exceeded.
And a third study by CDC researchers published in the Journal of the American Medical Association this week, three injections of mRNA vaccines were nearly 67% effective against symptomatic Omicron disease compared to unvaccinated.
Additional CDC data released this week also found that unvaccinated Americans over 50 were nearly 45 times more likely to be hospitalized than those who were vaccinated.
“Three doses of the original recipe appear to give good resistance to severe Omicron-induced COVID-19,” said immunologist and University of Toronto associate professor Jennifer Gommerman. “What we don’t know is how long it will last because Omicron is so different.”
Omicron has “strayed” from the original strain of the virus, Gommerman said, but mRNA vaccines are “very versatile” and manufacturers are already pivoting their formulations against.
“It makes sense that if we administer future doses, they would be tailored to trigger an immune response to Omicron,” she said.
“One of the reasons why healthy vaccinated people develop Omicron infections, which are sometimes accompanied by mild illness, is that the immune response must evolve toward recognition of this new variant.”
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Bhattacharya said while additional doses of the original vaccine formulation will provide additional protection against serious disease for those who need it, they will not completely control the spread.
“It could get you through the Omicron wave and maybe that’s the goal,” Bhattacharya said. “But our expectations should be pretty low as to what we can expect from these unparalleled boosters.”
The 4th dose may not be as effective
Israel has started offering a fourth dose to people over 60, immunocompromised people and healthcare workers, but preliminary unpublished hospital data found it to be largely ineffective in preventing Omicron infections.
“Beyond the third doses, it’s unclear what additional doses of the original recipe will do beyond temporarily boosting your antibody levels,” Gommerman said.
“I don’t think boosting everyone every few months to boost our antibody levels is a practical solution, especially since we know that three doses can generate sufficient immunity to prevent healthy people from developing severe COVID-19.”
Bhattacharya said if we had access to Omicron-compatible boosters in combination with protection against the original vaccine strain, we would be in a much better position to control the spread of the virus around the world – even if a new variant were to emerge .
“I think we’ll cover a lot more possibilities of what the virus could do next,” he said. “It won’t cover them all, but again, it might buy us a bit more time until the next thing.”
More “pretty certain” variants
Adapting vaccines to an evolving virus may seem complex, but it is not unheard of. The annual influenza vaccine, for example, is changed each year to match the influenza strains that are expected to be circulating in the coming season.
Alyson Kelvin, a virologist at the Canadian Center for Vaccinology and the Vaccine and Infectious Disease Organization at the University of Saskatchewan in Saskatoon, says vaccine makers need to think ahead to adapt long-term to emerging variants.
“That’s the headspace we need to be in…finding an appropriate scientific method to determine when COVID-19 vaccines need to be updated, and then the best way to implement and design them,” said she declared.
“This may be the last big push we have to deal with now. But I’m pretty sure we’ll see other variants appear and how those interact with humans, as well as our pre-existing immunity, there will be a lot of questions to answer.”
Ciriaco Piccirillo, an immunologist and principal investigator at the Research Institute of the McGill University Health Center and the Coronavirus Variants Rapid Response Network (CoVaRR-Net), said we may need variant-specific reminders on a regular basis.
“Although it’s a great idea and great news, it will be late. It’s a bit like chasing after a moving train,” he said. “The speed of the pandemic is much faster than we are capable of.”
Gommerman said he is moving towards developing, testing and deploying mucosal boosters – much like nasal spray vaccines used for influenza – can build on existing immunity and deploy immune cells to the upper respiratory tract to better prevent infection.
Canadian researchers at McMaster University have already started clinical trials for two inhaled vaccineswith plans to adapt their wording to new and existing variants.
“The combination of respiratory immunization and intramuscular immunization [with a needle] is most effective in creating a broadly protective response,” Kelvin added. “So primary intranasal, followed by an intramuscular boost.
Piccirrillo said that just as we need to anticipate variant-specific boosters, we need to start thinking about different methods of vaccine delivery.
“I think you’ll get much faster and much more effective immune protection against infections and hospitalizations,” he said. “It will have a huge impact.”
What will post-Omicron immunity look like?
But as the first signs give hope that Canada’s Omicron wave peaked, what will our population-level immunity look like after it crashes? And will that be enough to avoid a new wave of variants?
Piccirillo said Omicron will likely become the dominant endemic strain of the virus, meaning it could overtake future variants due to its high transmissibility and bring more immunity to the population through infection in addition to vaccines.
“Maybe there’s a silver lining to that cloud,” he said. “I think this increased infection rate is likely going to contribute directly to our much-needed herd immunity.”
But Kelvin warned that while Omicron can boost the level of immunity in the population among the vaccinated and unvaccinated – creating so-called “hybrid immunity” – it comes at a cost.
“We have to weigh this benefit against the unfortunate consequences of being infected with COVID-19,” she said. “Which could be long COVID or other pathological diseases that may arise.”
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Bhattacharya said that after this surge in COVID-19 levels drops, there will likely be a lot more immunity in the population to both the original virus and Omicron, and it looks like the immunity acquired by infection is “additive” to vaccines.
“On the one hand, Omicron is evolutionarily coming out of left field. It’s not a derivative of Delta, which a lot of us thought was the next thing to come,” he said.
“But I think Omicron immunity plus immunity to the original variant covers a lot of the possibilities of what the virus might do next.”
Could the virus still mutate into something even more transmissible or immune evasive than Omicron, jeopardizing the hard-fought immunity we’ve gained in the population?
“Of course. But it’s not unreasonable to hope that it will buy us a little more time,” he said. “Because boy, we really need it.”