she says. “I was just wiped out, had a little
bit of vertigo and had a headache, and I
never have headaches. I also had a little
fever. But the next day I was fi ne.”
Kelly takes her symptoms as a sign
that the vaccine did its job and that her
immune system is now primed to de-
fend against SARS-CoV-2. Data from a
subset of volunteers in the fi rst phase
of the studies seem to support that: the
new anti bodies they formed after getting
vaccinated appeared to neutralize lab-
based versions of SARS-CoV-2. Buoyed
by these early studies, Moderna began
a study in June to identify the ideal dos-
age, and at the end of July it launched the
fi nal stage of testing, which will include
30,000 volunteers who will receive ei-
ther that dose or a placebo.
The speed with which Moderna was
able to develop and start testing was a
tantalizing lesson in possibility for other
vaccine developers. Major players in the
pharmaceutical industry began prioritiz-
ing mRNA programs they had been de-
veloping with smaller biotech fi rms with
expertise in the technology. For exam-
ple, Pfi zer, the New York–based pharma
giant, took advantage of a two-year col-
laboration with German immunotherapy
company BioNTech and, in April, poured
$185 million into a joint eff ort to explore
four potential mRNA-based vaccines.
The two companies had been working
on using mRNA to create a fl u vaccine,
and when COVID-19 struck, says Philip
Dormitzer, vice president and chief sci-
entifi c offi cer for viral vaccines at Pfi zer,
“it was relatively straightforward to swap
out the infl uenza- coding antigens in the
vaccine candidate and put in COVID-19
antigens instead.”
Such substitutions are one of the
mRNA technology’s strongest features;
rather than requiring copious amounts
of live virus, all researchers need is the
virus’s genetic sequence, which they can
then edit to fi nd the right code for anti-
gens to alert the immune system of the
virus’s intrusion. Pfi zer and BioNTech
scientists exploited this and quickly de-
veloped four promising candidates for
testing; early studies identifi ed one,
containing the entire genetic sequence
of the virus’s spike protein, as produc-
ing the fewest side eff ects with the most
robust immune response. At the end of
July, the companies started a combinedfor human testing at the end of February.
Three months later, it had its fi rst batch
of data from a few dozen healthy volun-
teers in a small, early-stage trial. The vac-
cine appeared safe and seemed to prompt
the immune system to generate anti bodies
against SARS-CoV-2 in amounts similar to
those found in people who had recoveredfrom COVID-19. Kelly kept a diary of her
temperature and any unusual symptoms
for seven days after the fi rst shot, which
she says didn’t aff ect her much, and the
research team took weekly blood samples
until her second shot around three weeks
later. That injection hit her harder; “Oh
my golly, the next day I was exhausted,”... and the body’s defenses do the rest
ANTIGEN-
PRESENTING
CELL
T CELL
B CELL
ANTIBODIES
SARS-COV-2
MATCH
INNOVATIVE
(^3) Antigen-presenting cells
engulf spike proteins and
process them for immune
T cells and B cells to
recognize easily
(^4) B cells and T cells
work together to
release antibodies
that recognize the
unique spike shape
(^6) If a live SARS-CoV-2
virus enters the body,
immune cells recognize
the spike and work to
neutralize the virus
(^5) Antibodies quickly
bind to any spike
proteins, preventing
the virus from
infecting more cells
44 IN DEVELOPMENT
NONCOVID
VIRUS SHELL
SPIKE
GENE
A weakened form of the
common cold virus, loaded
with the genes for the SARS-
CoV-2 spike protein, infects
cells that then churn out the
protein, alerting the immune
system, which activates to
fi ght the infection.
ASTRAZENECA halted its
Phase 3 study after a report of
an illness on Sept. 9
0 1 2 3 4 5
VIRAL VECTOR
16 IN DEVELOPMENT
PLASMID
SPIKE
GENE
Snippets of coronavirus
DNA that code for the spike
protein are formed into a
circular structure called a
plasmid. Once inside human
cells, plasmids can make
copies of the spike protein to
alert immune cells.INOVIO has worked on DNA
vaccines for a decade, but
none have gone to market yet0 1 2 3 4 5
DNA PLASMID
23 IN DEVELOPMENT
LIPID
CAPSULE
mRNA
WITH
SPIKE
SEQUENCEThis approach is similar to
the DNA method but uses a
different form of the virus’s
genetic code, called mRNA.
Once the delivery system
gets it into human cells, it
starts to make copies of the
spike protein.MODERNA was the fi rst to
start human testing, but its
vaccine must be stored frozen