New Scientist - USA (2021-02-13)

14 | New Scientist | 13 February 2021

THE race to develop vaccines

against covid-19 got off to a flyer,

but with dangerous new virus

variants, stark inequalities

in access to vaccines and few

vaccination options for children,

the world still needs all hands on

deck. Last week, a virtual meeting

run by the New York Academy of

Sciences called The Quest for a

COVID-19 Vaccine showcased the

most promising new candidates.

Codagenix: A nasal spray

So far, all approved covid-

vaccines have been injectable.

Another option is a nasal spray,

says Robert Coleman, CEO of

biotech company Codagenix,

in Farmingdale, New York.

Codagenix’s technology uses a

live, but weakened, version of the

coronavirus that causes covid-

to provoke an immune response.

This approach makes the company

the black sheep of the vaccine

community, admits Coleman.

“They are the most efficacious

form of vaccine, they are single

dose, they provide broad and

robust immunity, but most

people consider them to have

safety risks.”

The reason? Conventionally,

such vaccines are produced by a

trial-and-error process in which

the virus is grown in animal cells

until it acquires enough mutations

to make it harmless to humans.

Viruses in such vaccines

can occasionally revert back to

the dangerous type and start

circulating among people,

setting off new waves of disease.

However, Codagenix

synthesises its coronavirus

genome from scratch, and

introduces genetic changes that

weaken the virus. The enfeebled

virus can replicate sluggishly and

stimulate the immune response,

but doesn’t cause disease. The

team believes that the genome is

so heavily modified – it has 283

mutations compared with the

original virus – that there is no

risk of it reverting back to being

dangerous. “We call it death by

a thousand cuts,” says Coleman.

One advantage of this

approach is that the immune

system encounters the entire

virus, so mounts a broad response,

potentially allowing it to be

more effective against variants,

although this is yet to be tested.

The vaccine is administered

in a single dose dripped into the

nose. It is currently in phase I

trials (see “Trial phases explained”,

right). The vaccine will also be

tested on children, says Coleman.

Valneva: A whole,

inactivated virus

A vaccine developed by Valneva

in Saint-Herblain, France, leans

on past successes by containing

inactivated, whole virus, which

cannot replicate but still induces

an immune response.

Conventionally, such viruses

are inactivated using chemicals

or ultraviolet radiation. The

inactivated virus is then purified,

concentrated and mixed with

a substance called an adjuvant,

which boosts the response of the

immune system. It is a venerable

technology and commonly

used in many flu vaccines.

They are exceptionally safe,

says Thomas Lingelbach,

Valneva’s CEO, so the vaccine

could be given to vulnerable

populations such as those

at risk of an allergic reaction

from other types of vaccine.

The two-shot vaccine is

in phase I/II trials, with plans

for testing in children.

Inovio: DNA, not RNA

Two of the first crop of covid-

vaccines – made by Pfizer/

BioNTech and Moderna – use

messenger RNA (mRNA), which is

injected into muscle cells. The cells

then translate the RNA’s genetic

code and make viral proteins that

stimulate an immune response.

Both vaccines provide around

95 per cent protection against

severe covid-19. But the technique

has downsides, not least that the

mRNA has to be kept blisteringly

cold during distribution and has

a short shelf life once unboxed.

That is where DNA can

outperform mRNA, says

J. Joseph Kim, CEO at Inovio

Pharmaceuticals, in Plymouth

Meeting, Pennsylvania.

Inovio has synthesised a DNA

version of the coronavirus’s spike

protein gene – which is made of

RNA in the actual virus – and

inserted it into circles of DNA

called plasmids. These are blasted

into the skin using a reusable

“gun”. The DNA is taken up by

skin cells and transcribed into

mRNA, which is then translated

into “massive quantities” of

spike protein, says Kim, eliciting

a strong immune response.

DNA vaccines don’t require

frozen storage, and have a one-year

shelf life at room temperature and

up to five years in a refrigerator.

Inovio’s vaccine only contains DNA

and water, so is also less likely than

some other vaccines to provoke an

allergic reaction. Inovio’s two-dose

vaccine is in phase II trials.

CureVac: Natural RNA

Another twist on mRNA vaccines

is being developed by CureVac in

Tübingen, Germany. Both of

the existing RNA vaccines for

covid-19 use mRNA that has been

chemically modified so that it can

evade the defences of the innate

immune system, which degrades

foreign mRNA on the (usually

correct) assumption that it is

from a virus. Modification is

carried out by adding synthetic

nucleotides, the building blocks

of RNA, that aren’t found in nature.

However, these modifications

dampen innate immunity. This is

“A vaccine in pill form is
in development that could
be delivered by post. The
vaccine comes to you”

New vaccines

From top left, clockwise:

Vaxart’s pills, CanSino

Biologic’s child-friendly jab,

CureVac’s RNA vaccine,

Codagenix’s nasal spray

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Tomorrow’s vaccines

The world needs new vaccines to beat nasty coronavirus variants, overcome delays

and solve global inequality. Graham Lawton investigates what’s in the pipeline

News Coronavirus