In the coming days, people in the US and UK will be among the first to receive a new breed of COVID-19 vaccine. The hope was that these updated vaccines – based on variants of Omicron – will offer significantly better protection than older vaccines based on the virus that emerged in 2019. But an analysis1 suggests that the updated boosters appear to offer about the same protection as an extra dose of older vaccines, especially when it comes to keeping people out of hospital.
“It’s not some sort of super shield against infection compared to what you might have gotten two weeks ago or a month ago,” says John Moore, a vaccine specialist at Weill Cornell Medicine. in New York who did not participate in the modeling. study, published on the preprint server medRxiv on August 26. US and UK regulators should have considered the potential effectiveness of updated vaccines before authorizing them, Moore argues.
On August 15, the UK became the first country to approve these “bivalent” vaccines, based on the Omicron BA.1 line and the original SARS-CoV-2 sequence identified in Wuhan, China, and will roll them out soon. . And this week, the US government is expected to give the green light to similar bivalent vaccines.
Small efficacy trials
Large-scale efficacy trials have shown that the first generation of COVID-19 vaccines reduced disease risk by more than 90%. But such studies — which involved randomly assigning tens of thousands of people to receive a vaccine or a placebo and tracking who got infected — are no longer practical, possible or ethical in 2022.
Updated COVID vaccines have instead been tested in smaller groups. To assess effectiveness, developers typically measure participants’ immune responses, specifically infection-blocking “neutralizing” antibodies, and compare them to those of people who received another dose of the original vaccine.
Most of these trials found that updated vaccines – based not only on Omicron, but also on older variants, including Beta – performed somewhat better in this measure than the original vaccines. “This is a clearly superior booster,” Moderna Chairman Stephen Hoge told investors on June 8, touting the results of the company’s bivalent BA.1-based vaccine.
To try to make sense of findings like Moderna’s, a team led by Deborah Cromer, a mathematical modeler at the University of South Wales (UNSW) in Sydney, Australia, collated all of the vaccine trial results. they could find, as well as fourth-dose studies of the initial vaccine.
Both types of vaccines caused antibody levels to skyrocket, but updated versions did so at levels on average 1.5 times higher than older vaccines based on the original SARS sequence. -CoV-2. “We’re not talking about a radical change,” Cromer says.
Studies suggest that higher levels of neutralizing antibodies equate to better protection against COVID. But the updated vaccine trials were unclear how much more effective they might be.
To determine this, Cromer’s team applied a model she, UNSW immunologist Miles Davenport and their colleagues developed by relating the effectiveness of the original COVID-19 vaccines to antibody levels.2. The model found that most of the benefits of updated vaccines come from getting an extra dose of any vaccine.
For example, in a population where half the people are already protected against symptomatic SARS-CoV-2 infection through previous vaccines and infection, an updated vaccine booster increased protection by up to 90 %, compared to 86% protection provided by an additional dose of the original vaccine. For protection against severe disease, the differences in protection were a few tenths of a percent (see “How COVID boosters measure up”).
At the population level, updated vaccines could make sense. Cromer’s team estimated that, per 1,000 people, a booster campaign based on updated vaccines would result in an average of 8 fewer hospitalizations than a campaign based on older vaccines. “If that translates to hospital beds saved and serious cases averted, that might be enough of a level to warrant recommending a modified recall variant,” she says.
The relative advantages of variant-based boosters could increase, when pre-existing immunity suddenly becomes weak due to a new variant (see “Immunity Matters”). It happened in December with the emergence of Omicron – and could happen again. In this scenario, an Omicron-based vaccine could provide much better protection than older ancestral vaccines, Cromer says.
Long term benefit
When the US recall campaign started, it decided to use a different Omicron vaccine than the UK-approved one. In June, a US Food and Drug Administration (FDA) advisory committee asked companies to develop bivalent vaccines based on the original strain and the BA.4 and BA.5 variants of coronaviruses – which have identical spike protein sequences – instead of the bivalent BA.1 vaccine that has been tested by Moderna, Pfizer-BioNTech and others. The hope was that by better matching circulating strains, vaccines would prove more effective.
But Cromer’s analysis suggests the differences may be trivial. Even updated vaccines based on Beta and Delta variants should protect against BA.4 and BA.5 infections almost as well as vaccines based on these variants. Similarly, bivalent vaccines that included the original vaccine appeared no more effective than vaccines based only on a newer variant.
For these reasons, the FDA’s decision to reject a BA.1-based recall probably wasn’t worth it, Cromer says, especially as SARS-CoV-2 continues to evolve. “It doesn’t seem to suggest that it’s going to give a dramatic improvement in booster vaccine efficacy to have this slight change.”
Dean Follmann, a statistician at the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, says even the marginal benefits of a vaccine based on BA.4 and BA.5 might be enough to justify their deployment. “It’s probably a little better. Much better – probably not. Moreover, he says the main message of the analysis should be that any COVID-19 reminder is good.
Other scientists question the decision to pursue variant boosters when the benefit is so small. Moore worries that people could be misled into thinking that updated vaccines are much more effective than existing vaccines, and could then put themselves at greater risk of infection.
Paul Offit, a vaccine specialist at Children’s Hospital of Philadelphia in Pennsylvania, who was one of two members of an FDA advisory committee to vote against the COVID-19 vaccine update, says the Cromers’ analysis underscores his skepticism. “If this vaccine is not more effective than current vaccines, then why distribute it,” he says. “You’re going to have very little impact on the incidence of serious illnesses.”
In the long term, it probably makes sense to develop vaccines based on variants, Cromer says, but the idea that they have to closely match circulating virus strains is unrealistic — and counterproductive when highly effective vaccines are already available. . “The most important vaccine booster is the one you actually get.”
. new specific vaccines Omicron offer protection similar to existing boosters