Time September 21/September 28, 2020Phase 2 and Phase 3 trial of this candi-
date with 30,000 people.
Pfizer isn’t the only company to fast-
track stakes in the mRNA technology. In
June, Sanofi increased its investment in
Translate Bio, which could total up to
$1.9 billion and give Sanofi access to the
technology and manufacturing know-how
to develop mRNA-based vaccines against
infectious diseases—with COVID-19 the
obvious priority. The companies are work-
ing on starting clinical trials in people
sometime this year.
But while the mRNA platform may
give vaccine makers a jump-start in de-
velopment, more familiar vaccine ap-
proaches have well- established manufac-
turing and storage methods behind them.
For one thing, mRNA is notoriously unsta-
ble and sensitive to temperature, so vac-
cines made with this technology need to
be stored and shipped at anywhere from
–94°F (–70°C) to –4°F (–20°C), far below
temperatures required for most exist-
ing vaccines. That’s why companies like
Sanofi, Johnson & Johnson and Astra-
Zeneca are relying on their experience
with another innovative but promising
vaccine- making method to solve that
problem—one that involves another virus.
Because viruses are adept at infecting
cells, they can be a useful vehicle for trans-
porting other viruses to prime the body’s
immune cells, as long as they are disabled
first. Drug companies are building and
testing vaccines against Ebola, influenza
and RSV, among others, by Trojan- horsing
genetic material from one virus inside the
shell of another that isn’t able to cause dis-
ease, but questions remain about how safe
such double- virus vaccines might be.
At Johnson & Johnson, based in New
Brunswick, N.J., scientists are counting on
a weakened form of adenovirus, which is
responsible for the common cold, to de-
liver COVID-19 material. Its team hopes
that its shot, unlike many of the other
COVID-19 vaccine candidates, will re-
quire just one dose. The company plans
to test both single and double doses of its
vaccine in beginning in September.
In the U.K., scientists at the Univer-
sity of Oxford are using a similar approach
for their vaccine, which will be devel-
oped, manufactured and distributed by
Astra Zeneca. They inserted the genetic
code for SARS-CoV-2’s spike protein
into a weakened cold-virus vector that
normally infects chimpanzees. The cold
virus transports the viral genetic material
to human cells and “infects” them in the
same way SARS-CoV-2 would, and there-
fore prepares the immune system to at-
tack it in much the same way a natural
infection does. In early human studies,
the vaccine produced good immune re-
sponses against SARS-CoV-2.
The Oxford- AstraZeneca team be-
lieves its manufacturing process for this
sort of shot will make it easy to scale up
production. “Hopefully, if it’s successful,
this vaccine will be relatively inexpensive
to make in terms of dollars per dose, and
it’ll be relatively easy to do at scale,” says
Mene Pangalos, executive vice president
of bio pharmaceutical research and devel-
opment at AstraZeneca.
There may be a price for that manufac-
turing ease, though: relying on vectors like
the one for the common cold can cause
problems down the road. First, the expo-
sure to two viruses, even if one is weak-
ened, could trigger an excessive immune
response that ends up causing more in-
flammation that could be harmful rather
than helpful. Second, while cold viruses
are, at first, adept at infecting cells, human
immune systems are also adept at learn-
ing to rebuff them. So while a cold-virus-
based vaccine may be effective at initially
generating an immune response against
SARS-CoV-2, if someone is exposed again,
that immune response might not be as ro-
bust the second time. This is a real public-
health concern, since most officials are
bracing for a wave of new cases in the
fall and winter when flu cases also peak.
The trial, which AstraZeneca was ex-
panding to include 50,000 people in the
U.S., U.K., Brazil and South Africa, is cur-
rently suspended as researchers investi-
gate whether an illness experienced by
one of the study volunteers is related
to the vaccine. The unexplained illness
was reported as part of routine safetymonitoring done by independent review
boards that are part of each major vaccine
trial to ensure that the new vaccines don’t
cause more harm than good.in some ways, the pause in the trial may
also serve as a testament to the value in
sticking with more proven strategies that
have a legacy of success. Researchers also
know from experience that another gene-
based approach, one that relies on DNA,
can generate not only antibodies against
a virus like SARS-CoV-2 but also T cells
and B cells, which help the body establish
a longer-lasting memory of previous in-
fections and better prepare it to recognize
and target viruses and bacteria should they
invade again. While antibodies generated
against SARS-CoV-2 proteins are likely to
be an important ingredient in the ultimate
alchemy of immunity, there are hints from
recovered COVID-19 patients that those
antibodies may not always be enough.
Recent analysis of convalescent plasma
from recovered COVID-19 patients in New
York, for example, shows that their levels
of antibodies vary widely and that most of
these antibodies have only moderate pow-
ers to neutralize SARS-CoV-2, at least in
the lab. In addition, some studies suggest
that the level of antibodies can wane as
quickly as three months after infection.
For a more durable and lasting pro-
tection against future infections, the
body needs to enlist the help of its cell-
mediated immune response, includ-
ing T and B cells, which have the ability
to remember, recognize and reactivate
against previous foes. While Moderna
has reported that its mRNA vaccine gen-
erated good T-cell responses, DNA-based
vaccines against other diseases have al-
ready proven adept at this job.
In part, that’s what attracted Sanofi to
partner with GlaxoSmithKline (GSK) for
another potential COVID-19 shot called a
recombinant protein-based vaccine. The
approach involves taking the genetic code
for parts of SARS-CoV-2’s spike protein
and, in Sanofi’s and GSK’s case, inserting
them into insect cells that then serve as
the factory for producing the viral protein.
Researchers then extract and purify this
protein and combine it with a GSK com-
pound that, when injected, prompts the
human immune system to generate de-
fenses, specifically antibodies, against it.
It’s a reliable technique, and responsibleScience