ant has brought a broader debate to a
head: how to handle future COVID-
waves as we move further down the Greek
alphabet of SARS-CoV-2 variants. “The
idea of reboosting every 6 months or even
every year, that’s not a public health strat-
egy,” says epidemiologist Céline Gounder
of New York University’s Grossman School
of Medicine.
Paul Offit, a pediatrician at the Chil-
dren’s Hospital of Philadelphia, contends
it’s “extremely unlikely” Omicron will
make healthy, vaccinated people under age
65 very sick because it can’ t outfox T cells—
which early studies suggest are largely un-
affected by this variant’s mutations—and
immune memory. The current vaccines,
he notes, have shown 90% or better pro-
tection against severe disease, “as defined
by the likelihood of having to
visit a doctor, go to the hospi-
tal, or worse,” he says.
In expecting SARS-CoV-
vaccines to protect against
transmission as well as mild
and moderate disease, “we’re
holding this vaccine to a dif-
ferent standard,” Offit says. He
doesn’t think giving booster
shots to entire populations—as
most countries that can afford
it are now doing at breakneck
speed—is necessary.
Gounder, though, argues a
booster push currently makes
sense because there are so
many unknowns about Omi-
cron’s severity (see p. 1543).
“Let’s give third doses right
now to buy us some time
while we sort it out,” Gounder says. It’s
also possible that boosting will reduce the
incidence of Long Covid, a still-mysterious
constellation of persistent symptoms that
can arise after even a mild initial infection.
For now, vaccine boosters rely on the
same formulations and doses authorized
before Omicron arrived. But Moderna,
which received authorization from the U.S.
Food and Drug Administration (FDA) to
cut its current dose in half for the third
booster shot of its mRNA vaccine, is run-
ning a clinical trial of a full-dose booster
to see whether it produces higher levels of
antibodies against Omicron.
It and other vaccine developers are
also creating variant specific updates of
the currently authorized shots—which all
are derived from the original SARS-CoV-
that circulated in Wuhan, China, in early- Moderna and the other producer of
a widely used mRNA vaccine, Pfizer and
its partner BioNTech, say they could begin
to deliver an Omicron-tailored vaccine as
soon as March. But they warn that shifting
to a new vaccine would cut production of
the current one.
Moderna has tested the impact of mRNA
mixtures that combine the original variant’s
spike with new ones, and suspects this might
provide broad enough protection to counter
Omicron. Pfizer and BioNTech reported last
week that in a clinical trial, a boost with an
mRNA vaccine coding for the spike of an ear-
lier variant, Alpha, elicited neutralizing anti-
body levels against Omicron more than four
times higher than boosts with spikes from
Beta, Delta, or an Alpha/Delta mix. “The
Omicron variant shares multiple mutations
with the Alpha variant,” explained BioNTech’s
CEO, Ug ̆ur S ̨ahin, at a press briefing.
Regulatory hurdles remain unclear: Will
FDA or other regulatory bodies simply acceptevidence of immune responses correlated
with COVID-19 protection rather than wait
perhaps months for clinical trial proof? An
analysis of the Moderna’s original vaccine ef-
ficacy trial found neutralizing antibodies ac-
counted for only 68% of the protection. Still,
Peter Marks, who heads the vaccine division
at FDA, says, “Immunogenicity studies based
on neutralization assays will suffice for a
[vaccine] change if we need it.”
Immunologist John Moore of Weill Cor-
nell Medical College, who favors boosting
as many people as possible with the current
mRNA vaccines, calls it prudent to do the
preliminary work on Omicron-focused vac-
cines, but suggests by the time they’re scaled
up, the Omicron wave may be over.
“Maybe we are too late for the first wave,
but if Omicron is here to stay, we need a spe-
cific vaccine,” Krammer counters. “I think not
acting is problematic.”
Moore also remains wary of companies,
which could benefit financially from variant
boosters, steering vaccine policy. “It is goingto have to be based on as much data as pos-
sible, and some very serious discussions in
the high levels of the administration, without
the company execs putting their finger on the
scales,” he says.
Nicole Lurie, who heads the U.S. division
of the nonprofit Coalition for Epidemic Pre-
paredness Innovations (CEPI), also sees no
need for an Omicron-specific shot given its
rapid spread, but says the companies should
be prepared to make vaccines for mutants
that move more slowly. “Or they have to get
faster at making vaccines,” she says.
Lurie and others say Omicron has under-
scored the need for vaccines that protect
against all severe acute respiratory syndrome
(SARS)-related viruses—known collectively
as sarbecoviruses—or, better yet, all viruses
in the coronavirus family. CEPI in March
put out a call for proposals to
develop such vaccines, hop-
ing to put $200 million toward
such projects over the next
5 years. The U.S. National Insti-
tute of Allergy and Infectious
Diseases (NIAID) in Septem-
ber announced grants totaling
$36.3 million to university
teams that have the same goal.
“It’s a compelling need,” says
NIAID Director Anthony Fauci,
a co-author of a perspective last
week on the topic in The New
England Journal of Medicine.
A pancoronavirus vaccine
may not be as tall an order as
it might seem, says Fauci, who
takes heart in the fact that cur-
rent vaccines have powerfully
prevented severe disease with
all variants. “That bodes pretty well for the
possibility of getting a pancoronavirus [vac-
cine] that you can boost with and protect
against everything,” he says. Already, several
have fared well in animal trials.
Some vaccinated people may already
have pan-sarbecovirus antibodies, a team
led by Linfa Wang of the Duke-NUS Medi-
cal School in Singapore found. Wang’s team
has studied people who had survived SARS
nearly 2 decades ago and recently received
COVID-19 mRNA vaccines. In test tube stud-
ies, their antibodies neutralized the corona-
virus that causes SARS, SARS-CoV-2, and
several related viruses found in bats, the
group reported in August.
Wang is now making a vaccine booster
based on a hybrid of spike sequences from
SARS-CoV and SARS-related bat viruses. But
he doesn’t have access to monkeys to rigor-
ously test the concept first and still needs
a corporate partner to back the project, he
wrote in an email. “The Omicron emergence
PHOTO: AP PHOTO/PAUL WHITE will hopefully make this move a bit faster!” j
SCIENCE science.org 24 DECEMBER 2021 • VOL 374 ISSUE 6575 1545COVID-19 vaccine shots are prepared in Spain, one of many countries rushing to deliver
booster doses to thwart the Omicron variant.