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Briefing NEWS 15

28 March 2020 THE WEEK

Howwerevaccinesdeveloped?
ThereisevidencethatChinesephysicians
wereinoculatingagainstsmallpoxas
earlyasthe17thcentury:theyblew
powderedsmallpoxscabsupthenose
ofpatients,toprotectthemagainstthe
disease.Inthe18thcentury,itwaswidely
usedinTurkey:LadyMaryWortley
Montagu,wifeoftheBritishambassador
totheOttomanEmpire,spreadtheidea
toBritain,withheraccountsofchildren
being“engrafted”withsmallpoxpus.
Thetreatmentwasfine-tunedbythe
BritishphysicianEdwardJenner.He
hadheardthatdairyworkerswhohad
contractedcowpox,orvaccinia,amilder
formofsmallpox,nevergotthedisease.
Sohetookpusfromamilkmaidwith
cowpox,andscratcheditintotheskinof
ayoungboy.Jennerlatertriedtogivethe
boysmallpox,andnotedthathewasimmune–orvaccinated.

How do vaccines work?
Traditionalvaccinespresentpartorallofthe virus (orbacterium)
to the humanimmune system,usuallyin theform ofaninjection
at alow dose, topromptthesystemtoproduceantibodiestoit.
Antibodiesareakind ofimmune memorywhich, havingbeen
generated once,canbe mobilised againquicklyifexposed tothe
virus. This is usually done usingalive, weakened form of the virus,
oravirus which has been inactivatedby heatorchemicals;inthe
past such viruses hadto beculturedto produce suchtreatments,
on chicken eggs or human cells. Today, there are new, faster–and
lessproven –gene-basedapproaches.Scientiststryto liftsections
ofavirus’sgeneticcode and putitintoother, harmless,viruses;
or toinjectsegmentsofDNA orRNAintothebody,sothatour
cells are encouragedtoproduceantibodies againstit.Eitherway,
thechallengeisthesame:devisingavaccinestrong enoughto
confer immunitywithoutmakingthe individualseriouslyill.

Who is working onacoronavirus vaccine?
Thisislikelyto beoneofthefastest vaccineeffortsinhistory;
about35 companiesand academicinstitutionsare racingtocreate
one. China sharedthevirus’sgeneticsequenceswiftlyinearly
January,andmuchwork hadalready
begunontwoothercoronaviruses
whichhadcausedrecentepidemics:
Sarswhichshares80%ofthe Covid-
19 virus’s geneticmaterial.Various
vaccine“candidates”are already up
and running. In Seattle,45volunteers
havereceivedanexperimentalgenetic
vaccinemade by the US biotechfirm
Moderna as partofapreliminary
safety trial.OxfordUniversity’s
JennerInstitute is working “with
greatcare, and duehaste”, on a
traditional weakenedvirus vaccine;
it is being testedon animals. Inovio
of SanDiegowants totest its vaccine
on humans nextmonth. China has
mounted avast scientific effort, and
hasstarte dclinical trials.

How are vaccines trialled?
Usually, they are testedfirst on
animals. Then there arethree phases
of human testing. First, usingafew
dozen healthyvolu ntee rs, the vaccine

willbetestedforsafety.Thesecond,ina

partoftheworldaffectedbythedisease,

looksathoweffectiveitisinseveral

hundredpeople.Thethirddoesthe

sameinseveralthousandpeople,looking

atitsefficacyandlesscommonreactions.

Inanemergency,someoftheredtape

canbestrippedaway.But“whilethereis

apushtodothingsasfastaspossible,it’s

reallyimportantnottotakeshortcuts”,

DrBruceGellinoftheSabinVaccine

InstitutetoldTheGuardian.

Whycan’tyoutakeshortcuts?

Rushingthingscouldresultinavaccine

that’sactuallyharmful;therehavebeen

casesinwhichpeoplewhoreceived

avaccinebecamesickerwhenthey

contractedthevirusitself.Inthe 1960 s,

acoldvaccinewasfoundtoaggravate

symptoms;asimilareffectwasfoundinoneexperimentalSars

vaccine. In 1976 ,25%of Americanswereinoculatedagainst

aswinefluoutbreak,causingseverereactions–the vaccine

probablykilledmor ethantheswine flu.Forthese reasons,

takingavaccineallthe way toregulatoryapprovalusuallytakes

adecade.Expertsarenear-unanimousthateven the accelerated

processwilltake12to 18months.

Butcoulditthenbeshippedoutquickly?

No,becauseitwillthe nneedtobemanufactured invast

quantities. Therearerelativelyfewglobal manufacturers,and

anynew vaccinethatworksissuretobe inshortsupplyas

governmentstrytoensure that their own peoplearethefirst

inline.TheUK isaleader invaccinescience,butlacksmass

manufacturingfacilities.It hasonlytwomajorvaccine factories,

runbyAstraZenecaandSeqirus;GSK, agloballeader,makes

itsvaccinesin Belgium.“If acountryhasafactorytomakea

vaccine, thefirst peoplethat willhavethatvaccinewillbetheir

citizensand theirhealthcareworkers and vulnerable people,” said

DrAl Edwards,abiomedical expertat theUniversityofReading.

Thereisadefinitepossibility that thepandemic willhavepeaked

and declinedbeforeavaccine iswidelyavailableinthiscountry.

So is it allpointless?

Notatall.Avaccinecouldstill

savemanylives, especiallyifthe

coronavirus becomesendemicor

perennially circulates,like flu, with

seasonal outbreaks. It’salso a

consolationthat, in thewakeofthe

Ebolaepide micinWestAfrica ,great

steps have beentaken to overcome

the twomajorproblemsin vaccine

production: that they take years to

developandmanufacture, andthat

they becomeobsolete if the virus

evolves–which means that pharma

companieshave beenloath toinvest

in them. The Coalitionfor Epidemic

Preparedness Innovations,backed

by nationalgovernments andprivate

philanthropists,is the largest vaccine

development initiativeeverunder-

taken.Inrecentyears ,vaccinescience

hastakenleaps and bounds:and in

the long term,auniversal vaccine for

all coronaviruses,notjustthe 2019

one,is now seriouslyinprospect.

The silver bullet: searching for avaccine

Scientistsaroundtheworldareworkingonavaccineforthecoronavirus.Howlongwillittake?

Montagu:dispatchesfromtheOttomanEmpire

Beyondthe vaccine

There are currently no “specific treatments” for Covid-

19. Doctors can only offer supportive care: making sure
    the patient is getting enough oxygen, usingaventilator
    if necessary, managing fever, treating secondary
    bacterial infections. However, there are some antiviral
    drugs available which may ultimately do more than
    vaccines to combat the disease. The World Health
    Organisation is launching global “mega-trials” on four
    of the most promising therapies, which may slow or
    kill the novel coronavirus: an experimental antiviral
    compound called remdesivir; the malaria medications
    chloroquine and hydroxychloroquine;acombination
    of two HIV drugs, lopinavir and ritonavir; and that
    same combination plus interferon-beta.
    Another key step in beating the pandemic could be an
    antibody test, which detects not just if someone has
    the disease, but whether they have ever had it. In
    theory, these could allow people who have built up
    immunity to return to their everyday lives. Last week,
    the Icahn School of Medicine in New York published
    an antibody test that they have developed, and
    directions for replicating it. The Government has
    ordered 3.5 million testing kits, with Boris Johnson
    describing it asa“gamechanger”.