The evidence is in: booster jabs against COVID-19 do provide an extra layer of protection against the illness. But questions still swirl over how much they’ll help and how often they’ll be needed — and the discovery of the Omicron variant has supercharged the debate over their role.
Real-world data from Israel1,2,3 and the United Kingdom4 indicate that a booster dose of one of the widely used mRNA-based vaccines sharply lowers a person’s likelihood of catching SARS-CoV-2 and getting sick. And several months after Israel became the first country in the world to make boosters available to all, its daily case counts remain low.
Such data have helped to sway health authorities that were cool to the idea of boosters for all. Now, hoping to stay ahead of the Omicron threat, public-health officials across North America and Europe are urging all adults to get a top-up dose of vaccine. Variant-specific boosters are also in the works, but doctors are urging people not to wait: immunizations with available shots today could help ward off a surge of Omicron infections.
If the variant does undermine vaccine performance, extra protection against the virus might require four or more jabs, possibly with new vaccine formulations — sharpening questions over whether boosting will need to continue indefinitely. The Omicron variant has also further clouded forecasts of how booster campaigns will affect the pandemic’s trajectory.
“Unfortunately,” says immunologist Ali Ellebedy at the Washington University School of Medicine in St. Louis, Missouri, “we’re still living in uncertainty.”
Even before Omicron’s arrival, many global-health researchers opposed widespread booster campaigns while immunization rates remain abysmally low in large swathes of the world. Boosters have already spurred debate over issues of equity and prioritization of limited vaccine resources, and scientists worry that wealthy countries’ rush to offer more boosters in the face of Omicron will further exacerbate the global vaccine imbalance — a disparity that many health researchers say probably contributed to Omicron’s emergence and rapid spread.
Here, Nature takes a look at three burning questions that could shape booster policies as the world faces yet another new variant.
Will we need regular boosters?
Before Omicron, Ellebedy and many other immunologists thought that third doses would be sufficient. The immune-system players that remember previously encountered pathogens — memory B and T cells — were holding up well over time, and it seemed that most people with two or three doses of a COVID-19 vaccine would maintain long-term protection against severe disease and death.
“Our immune response to these vaccines is really robust if you are healthy. Barring any massive surprise variants, I don’t see any reason why we’d need to get a fourth dose,” Ellebedy told Nature just hours before the first news reports on Omicron.
The new variant could change the immunological picture. Among Omicron’s many mutations, few seem likely to compromise T cells’ ability to recognize the virus and attack infected cells, notes Alessandro Sette, a vaccine biologist at the La Jolla Institute for Immunology in California. “But these are early days,” he warns, and many more experiments are needed to assess the variant’s impact.
Even if the body’s immune forces stays strong and vaccinated individuals remain shielded from the worst ravages of COVID-19, public-health concerns could warrant extra boosters down the line, possibly on a fairly regular basis.
For example, if community-transmission rates remain high, then extra doses of vaccine could control viral spread by elevating the number of ‘neutralizing antibodies’ that directly stop the virus from entering cells. Levels of these antibodies fall over time after vaccination, limiting their ability to suppress waves of infection. If Omicron turns out to be highly communicable, boosters could be especially useful: they tend to elicit a broad array of antibodies, at least some of which should maintain activity against the Omicron variant.
If they don’t, however, vaccine makers have a back-up plan: at least four companies have started developing Omicron-specific booster candidates. It will take months before any of those come to market, so public-health agencies continue to recommend standard boosters for the time being.
Will boosters help to curb the pandemic?
Judging by the Israeli experience, the strategy seems to be working. Before its mass booster campaign, the country — rocked by the double whammy of the Delta variant and waning immunity — had one of the highest daily infection rates in the world. Case counts are now well below their September peak. And although some triple-vaccinated individuals have tested positive for Omicron in recent days, their symptoms remain mild and there is no evidence of runaway viral spread.
“We are not yet seeing any reduction in the effectiveness of the boosters,” says Dvir Aran, a biomedical data scientist at the Technion — Israel Institute of Technology in Haifa.
Research in the past few months suggests that other places could have similar success. Disease ecologist Marm Kilpatrick and his graduate student Billy Gardner at the University of California, Santa Cruz, modelled the impact of booster initiatives on transmission dynamics, taking into account factors such as vaccination coverage and previous levels of infection.
Based on national estimates from the United States, where around 60% of individuals are fully immunized and around half of the population is thought to have a positive infection history, the researchers found that a broad booster push such as the one now recommended by federal officials could decrease the virus’s reproduction number, Rt, which is the number of people an individual with COVID-19 can go on to infect, by around 30%5.
In the United States, Rt is currently hovering at around one — any higher and the outbreak should grow, any lower and it should shrink. According to Kilpatrick and Gardner’s calculations5, boosters should therefore help to move case numbers downwards, thus buttressing against any upward pressure from Omicron.
“It’s not going to stop a raging epidemic,” Kilpatrick says. “But it definitely can take an epidemic that's growing at a very uncomfortable rate for lots of people, and make that into either a shrinking epidemic or a much, much less bad one.”
Projections in the United Kingdom also found that extra shots can help bend the pandemic’s curve. “We were walking towards what could have been quite a large outbreak if we didn’t do boosters,” says Matt Keeling, a mathematical epidemiologist at the University of Warwick, UK.
Modelling by Keeling and his co-authors found that if third doses generate lasting protection, then boosters should reduce COVID-19 hospitalization rates in England and keep them below current levels for at least two years6. But if protection wanes more quickly, boosters might have to be taken every 6 to 12 months to avoid surges in hospital admissions and deaths. Keeling’s work, like Kilpatrick’s, has been published as a preprint but not yet peer reviewed.
Are booster campaigns in high-income nations slowing efforts to vaccinate the rest of the world?
Manufacturers worldwide are currently producing an estimated 1.5 billion doses of COVID-19 vaccine per month, so in principle it should be possible to offer boosters in wealthier countries without hampering the supply of first and second shots in places with low immunization rates.
“The problem is that most of those doses are concentrated in certain parts of the world and are not getting to where they’re needed most,” says Andrea Taylor, a health-policy researcher at the Duke Global Health Institute in Durham, North Carolina. And until the world addresses issues such as delivery logistics, equitable prioritization and health-care infrastructure, the gap between vaccine haves and have-nots will only widen as rich nations hoard booster doses for themselves.
“Our generosity is compromised by the fear that we need a whole lot of boosters to give to our own populations,” says Madhukar Pai, an epidemiologist at McGill University in Montreal, Canada.
Even if the world has vaccines in abundance, trying to juggle booster campaigns in highly vaccinated regions with first-dose campaigns in unvaccinated ones is a daunting task. Inequitable vaccine roll-out “starts with an absence of leadership”, says Jerome Kim, director-general of the International Vaccine Institute in Seoul. “No one has an end-to-end vision.”
The public–private partnership called COVAX was meant to provide that strategic vision. But as Felix Stein, an economic anthropologist at the University of Oslo, has argued7, the initiative’s governance structure and dose-sharing strategies make it ill-suited for the job. “COVAX has zero checks, balances or enforcement mechanisms, either on countries in the global north who don't play ball or on the pharmaceutical industry,” he says.
Pai, for his part, says he is taking a “principled stand” and will forgo an extra shot if offered one (he currently does not meet eligibility criteria in Canada, which has yet to adopt a boosters-for-all policy). As long as so many people in lower-income countries remain unvaccinated, he worries, as do many other global-health researchers, that getting a booster sends the wrong signal about wealthy countries’ priorities during a pandemic.
Omicron should be a wake-up call about the need for collective action in response to the pandemic. But, says Pai, “I fear we are heading down a path where fundamentally nothing is going to change.”
Patalon, T. et al. JAMA Intern. Med. https://doi.org/10.1001/jamainternmed.2021.7382 (2021).
Bar-On, Y. M. et al. N. Engl. J. Med. 385, 1393–1400 (2021).
Barda, N. et al. Lancet https://doi.org/10.1016/S0140-6736(21)02249-2 (2021).
Andrews, N. et al. Preprint at medRxiv https://doi.org/10.1101/2021.11.15.21266341 (2021).
Gardner, B. J. & Kilpatrick, A. M. Preprint at medRxiv https://www.medrxiv.org/content/10.1101/2021.10.25.21265500 (2021).
Keeling, M. J. et al. Preprint at medRxiv https://www.medrxiv.org/content/10.1101/2021.11.05.21265977 (2021).
Stein, F. Global. Health 17, 112 (2021).