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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-


  1. 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”.

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