Will ‘forever boosting’ beat the coronavirus?

Now, faced with the extraordinarily contagious
omicron variant, Israel has begun offering fourth doses to some high-risk
groups. On Wednesday, the Centers for Disease Control and Prevention expanded
eligibility for boosters to adolescents and backed away from describing anyone
as “fully vaccinated” because two shots no longer seem adequate.

Instead, one’s vaccination status will now be
“up to date” — or not. It’s no surprise that many Americans are wondering:
Where does this end? Are we to roll up our sleeves for booster shots every few

Humbled repeatedly by a virus that has defied
expectations, scientists are reluctant to predict the future. But in interviews
this week, nearly a dozen said that whatever happens, trying to boost the
entire population every few months is not realistic. Nor does it make much
scientific sense.

“It’s not unheard-of to give vaccines
periodically, but I think there are better ways than doing boosters every six
months,” said Akiko Iwasaki, an immunologist at Yale University. Other
strategies, she said, could “get us out of this forever-boosting kind of a

For starters, persuading people to line up for
shots every few months is probably a losing proposition. About 73% of American
adults are fully vaccinated, but so far just over a third have opted for a

“This doesn’t seem to be a sustainable
long-term strategy, for sure,” said Deepta Bhattacharya, an immunologist at the
University of Arizona.

Just as important, there are no data to
support the effectiveness of a fourth dose of the current vaccines. (The
calculus is different for people with impaired immune systems, who might well
benefit from a fourth dose.)

Booster shots undoubtedly increase antibody
levels and help to prevent infection — and, as a result, may relieve pressure
on the health care system by temporarily slowing the spread of the virus. The
experts all said that given the omicron surge, Americans should get a third
dose as soon as possible.

But the immunity boost is transient; already
preliminary studies are showing a decline in antibody levels just weeks after a
third dose. And even at peak antibody levels, the boost does not uniformly
prevent infection with omicron, which is less vulnerable to the body’s immune

“Even with that amount of antibody, it’s very
hard to stop the virus for very long,” said Shane Crotty, a virus expert at the
La Jolla Institute for Immunology in California. “It’s a much higher bar now
than before, and maybe an omicron-specific vaccine would do a better job.”

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Pfizer-BioNTech, Moderna and Johnson &
Johnson have all said that they are testing vaccines targeting omicron that may
become available in a few months.

“It doesn’t make sense to keep boosting
against a strain that’s already gone,” said Ali Ellebedy, an immunologist at
Washington University in St. Louis. “If you are going to add one more dose
after three, I would definitely wait for an omicron-based one.”

If the goal is to boost immunity against
omicron or future variants, other tactics would be better than continual boosts
of a vaccine designed to recognise the original virus, experts said.

Some research teams are developing a so-called
pan-coronavirus vaccine designed to target parts of the virus that would change
very slowly or not at all.

The current vaccines could be combined with
boosters of nasal or oral vaccines, which are better at preventing infection
because they coat the nose and other mucosal surfaces — the entry points for
the virus — with antibodies.

And simply allowing more time between vaccine
doses might also strengthen immunity, a lesson scientists learned in fights
against other pathogens.

Many experts were initially opposed to the
idea of a booster shot at all. Some believed the original vaccine regimens were
enough to keep most people out of the hospital, and that this should be the
true measure of a vaccine’s success.

Others felt it was unfair for wealthy
countries to hoard the vaccine for booster shots when millions worldwide had
yet to receive a first dose.

But the perspective shifted when scientists
saw omicron’s rapid and unrelenting march across the world. “Omicron really did
change my thinking about this,” said Scott Hensley, an immunologist at the
University of Pennsylvania.

He and others now support a third dose. But
they see little use in following Israel’s path and rolling out a fourth,
arguing that other parts of the immune system — like T cells and B cells — are
holding steady against the virus after three doses, and perhaps even after two.

While these immune cells cannot prevent
infection, they ease the severity of symptoms and keep hospitalisations low.

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“People that are vaccinated really are doing
very well in terms of hospitalisation,” said Michel Nussenzweig, an
immunologist at Rockefeller University in New York. Omicron has made it clear
that preventing all infections is a lost cause, he added.

If the vaccines prevented infection and spread
of the virus, regular boosters might make sense. “But with omicron, what’s the
point?” Nussenzweig said. “The endgame is keeping people out of the hospital.”

Last fall, Dr Anthony Fauci, the nation’s top
pandemic adviser, repeatedly spoke of the importance of preventing symptomatic
infections. But in recent days he, too, has been saying that it is
hospitalisations that truly matter.

In order to prevent infections, booster shots
must be exquisitely timed to a variant’s circulation in the population. Many
people who got a third dose early in the fall, for example, were left
vulnerable to omicron because the immune boost had already subsided.

Generally, people are told to get vaccinated
against influenza just before the virus starts circulating in winter. If the
coronavirus settles into a flulike seasonal pattern, as it seems possible, “you
can imagine a scenario where we simply give boosters before the winter each
year,” Hensley said.

Lessons from flu season also suggest that
frequent vaccination is unlikely to be helpful. Giving the flu vaccine twice a
year “has a diminishing return, and so it may not make sense to do vaccination
so frequently,” said Ben Cowling, a public health researcher at the University
of Hong Kong. “For the initial doses that people receive the responses get
better and better, but then there’s a turning point.”

“I think it’ll be difficult to get high uptake
with more frequent vaccinations,” he added.

Some experts have raised concerns that getting
boosters too often — as some people are doing on their own — may even be
harmful. In theory, there are two ways in which it could backfire.

Most immunologists now dismiss as improbable
the first possibility, in which the immune system is exhausted by repeated
stimulation — a condition called “anergy” — and stops responding to coronavirus
vaccines. “We’re not really seeing these weird memory cells that are indicative
of anergy or dysfunction,” Bhattacharya said.

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The second worry, called “original antigenic
sin,” seems more plausible. In this view, the immune system’s response is
tailored to the first version of the virus, and its responses to subsequent
variants are much less powerful.

With more than 50 mutations, omicron is
different enough from previous variants that antibodies made for the original
version of the virus struggle to recognise the latest version.

“We have enough clues that it could be a
problem,” said Dr Amy Sherman, a vaccine expert at Harvard University. “We’ve
certainly seen evolution in a short period of time.”

The speedy evolution of the virus occurs in
large part because it has access to huge numbers of human hosts. If cases
continue to accumulate at the current rate, or something close to it, the virus
may continue to amass major changes — meaning the vaccines might need to be
regularly updated.

But if the pandemic slows in most parts of the
world, it may limit opportunities for the virus to emerge in a radically
different form. And that’s an argument for helping other nations immunise their
populations rather than boosting our own, Hensley said.

Americans would also be better served by
adopting strategies other than vaccines to control spread of the virus, some
experts said. In the case of pneumococcus, for example, immunising children
indirectly protects older adults by limiting transmission.

Improving ventilation in schools would limit
spread of the coronavirus among children and all of their contacts, said Sarah
Cobey, an evolutionary biologist at the University of Chicago.

“If we just go back to how we were
prepandemic, and we don’t make any sort of lasting changes to schools, kids
could be proportionately driving a lot of transmission,” she said.

For the United States to adopt any strategy,
whether it is periodic boosters or other approaches, the Biden administration
must first define what it is trying to accomplish, experts said.

Preventing infections would require a very
different approach than preventing hospitalisations, for example.

“We’re going somewhere fast, but we don’t know
where we’re going,” said Natalie Dean, a biostatistician at Emory University in
Atlanta. “Whatever the future holds, it just needs to be clear what the goal

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