PHOTO: CHRISTINNE MUSCHI/REUTERS1142 10 JUNE 2022 • VOL 376 ISSUE 6598 science.org SCIENCEI
n 1959, German microbiologist Anton
Mayr took a strain of vaccinia, a poxvi-
rus used to inoculate against smallpox,
and started to grow it in cells taken
from chicken embryos. After several
years of transferring the strain to fresh
cells every few days, the virus had changed
so much it could no longer reproduce in
most cells from mammals. But it could still
produce an immune response that pro-
tected against smallpox.
Mayr had set out to study how poxviruses
evolve, but by accident he had produced a
potentially safer smallpox vaccine. Dubbed
Modified Vaccinia Ankara (MVA) becausethe original viral strain came from that
Turkish city, the vaccine had a short career.
“With smallpox eradicated in 1980, it disap-
peared into the freezer,” says Gerd Sutter, a
virologist at the Ludwig Maximilian Univer-
sity of Munich, who has studied Mayr’s vac-
cinia strain for decades.
Now, this virus, further weakened and
brought to the market by the Danish
pharma company Bavarian Nordic, may
become key to arresting the largest out-
break of monkeypox ever seen outside Af-
rica, which has already sickened more than
1000 people. It is the only vaccine licensed
anywhere for use against monkeypox, al-
though other, riskier smallpox vaccines
also appear to work. The United States, theUnited Kingdom, Canada, and several other
countries have already started to “ring” vac-
cinate, offering it to contacts of identified
monkeypox cases, including health care
workers and sexual partners. “MVA will be
very important in this outbreak because it
is a nonreplicating vaccine, which means
it doesn’t have the same side effect profile
as some of the other live [virus] vaccines”
being considered, says Rosamund Lewis,
technical lead on monkeypox at the World
Health Organization (WHO).
But what role the vaccine will ultimately
play depends on a host of factors: whether
those most at risk from infection can be iden-
tified and vaccinated, whether the vaccine is
as effective as hoped, and whether enough
is available to stop the burgeoning outbreak.
WHO has so far only backed ring vaccina-
tion—MVA is ideally given within 4 days
of an exposure but recommended for up to
14 days—but some scientists say it’s too dif-
ficult to reach the specific contacts people
had. They advocate broader vaccination
campaigns in the population most affected
so far: men who have sex with men (MSM).
Hundreds of millions of doses of small-
pox vaccine are stored around the world,
insurance against a possible release of the
dreaded virus by terrorists or in war, and
they are known to offer some protection
against monkeypox. A study in the Demo-
cratic Republic of the Congo (DRC) in the
1980s found that household contacts of
people sick with monkeypox were seven
times less likely to contract the disease if
they had been vaccinated against smallpox.
Yet the vast majority of existing smallpox
vaccines consist still replicating vaccinia.
These can cause rare but life-threatening
side effects such as a encephalitis or pro-
gressive vaccinia, the spread of the vaccine
virus to the whole body, to which immuno-
compromised people are vulnerable.
Although 66 people have already died of
monkeypox this year in African countries,
the recent cases in nonendemic countries
have mostly been mild. And many con-
tacts of those infected are living with HIV,
which could make them more likely to suf-
fer from vaccinia side effects. Given the
risks and benefits, “using these vaccines is
out of the question,” Sutter says.
Bavarian Nordic’s nonreplicating vac-
cine, marketed as Jynneos in the United
States and as Imvanex in Europe, sidesteps
some of the risk. So does a vaccinia-based
vaccine named LC16m8, licensed for small-
pox only in Japan, which also appears to
cause fewer side effects. “I believe theseIN DEPTH
Canada has begun to offer a monkeypox vaccine
made by Bavarian Nordic to select groups, including
contacts of known cases of the disease.NEWSMonkeypox vaccination plans
take shape amid questions
Favored shot is a seemingly safer smallpox vaccine, but
researchers debate how best to use it
INFECTIOUS DISEASEBy Kai KupferschmidtBanca do Antfer
Telegram: https://t.me/bancadoantfer
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