Coronavirus vaccine: The scientists urgently seeking coronavirus solutions – BBC World Service

published on July 9, 2020

Hello, you're listening to CrowdSciencefrom the BBC World Service This is theshow that takes your questions to thescientists that might have answers andso we're here at the University ofOxford's Nuffield Department of Medicineto meet the researchers who are tacklingthe issue of the moment and the sciencebehind it because of this question fromlisten EvelynHi CrowdScience, I'm Evelyn and I'm calling from Westminster Colorado in the United States I'd liketo know what scientists are researchingto help us combat the Covid-19 disease

In particular I've heard thatsome groups of people such as childrencould be infected without showingsymptoms and could unknowingly becarriers Is this the case? If so how canresearchers and health officials address this?Thanks Evelyn and everyone who sentus questions on this topic Producer Jenand I have gained access to some of thekey laboratories working against coronavirusI'm grateful to the scientistswho've let us in given how busy they are

Right now Coronavirus has changed boththe focus and the minutiae of theirworking lives Just listen to usnervously negotiating a handshakePeter Horby is Professor of emerginginfectious diseases at the Center forTropical Medicine at the University ofOxford He's one of a whole team ofresearchers working around the clock tofind out more about Covid-19 diseaseIt's a difficult area epidemicinfections because you have to move very

Quickly, because the outbreaks are prettyquick We've been working initially withcolleagues in China since 2nd of Januaryand it's been very full on Seven days aweek, often calls at midnight or later Sowhat are you working right now?So we're doing a few things We've been trying tocollect standardised clinical databecause a lot of the data that comes inis partial and it's quite biasedSo what you hear about is the sickest patientsin hospital but what you don't see is

All the patients in the community, or thepeople in the community, who've got acough and sniffles and get better and soyou end upusually with a rather dramatic pictureof this very serious disease with lotsof deaths and you really need tounderstand the full spectrum of illnessbecause there'll be a bunch of peoplewho get infected and don't get sick at allThere'll be a bigger bunch of peoplewho get infected and get a mild illness

And then the top of this iceberg are thepeople who get into a hospitalSo we've been trying to collect data to give usan idea of the full iceberg includingthe bit you can't see under the water Sowe've been working with colleaguesaround the world and with the World HealthOrganization on trying to collect that clinical dataIt feels like that mightbe key to why this novel coronavirus isspreading so much is that there's aproportion of people who suffer with it

Who don't actually technically suffer atall It's clear that it's you know verytransmissible, like a lot of respiratoryviruses, and a lot of people don't getvery sick and so they're not reallyaware they have infection and it'spassed on like that There may be sometransmission even before symptoms startbut it's likely that people are mostinfectious at the time that they start to feel symptomsOur listener Evelyn isinterested in people who display milder

Or no symptoms at all Particularlychildren Are there patients like that in the data?It's becoming clearer that youknow children do get infected but theyseem to generally either have no illness ora very mild illness There are somechildren who've got quite sick but therisk is quite low in that groupSo that's good news It's not yet clear howthey contribute to transmission of infectionSo in flu children are reallyimportant They really drive transmission

Of flu and so things like closingschools etcetera can have a big impactWith this coronavirus it seems that that'sprobably less the case, that children doget infected but because they're notvery symptomatic they're likely to beless infectious and so they pay less of arole in spreading infectionSymptomatic meaning coughs and sneezes that transmitthe virus on?Yes, so the more symptomatic you are the more infectious you're likely to be

Evelyn's question is right on the moneythen Particularly with Covid-19This strain of coronavirus can infectsome people without presenting anysymptoms for days If we trust the dataaround 30% could have almost no symptomsat all but others will be hospitalisedThis presents a challenge for researchersHow on Earth do you find thepeople with coronavirus whose bodies aregiving little to no clue that they'reharbouring it?

And that's where differenttypes of studies become useful so takingblood from the general population andlooking for antibodies which you getafter infection is really usefulbecause that's the only way you get afull picture of how many people wereinfected and then you get the idea ofthat full iceberg of how many people are infectedEpidemiology is not the onlything Peter and his colleagues are

Studying So we're going to come back tohim laterBut as he just mentioned, antibodies areanother part of a different vitalresponse to Covid-19 disease, which ishappening inside everyone who's infectedOur immune response Time to find animmunologist I'm Tao Dong I'm Professor of immunologyBumping elbows with me isProfessor Tao Dong She's director ofthe Chinese Academy of Medical SciencesOxford Institute Originally from China,

How did she end up working in Oxford?That was a very, very long time ago28 years ago I came here with my husbandand then I started my d-phil study at OxfordAnd now has life here changed in thepast couple of months because of thecoronavirus outbreak? Yes very much Tobe honest I didn't sleep very well sinceit started because I come from China sowe get very updated information fromcolleagues and friends and at all levelsand really professionals and world

Leading expert in China and some justour friends and family with no knowledgeabout immunology or science,like grandparents, uncles, auntiesEverybody is worried And they're alltexting you? Oh this is your field Ithink because it's completely new virus anda new thing,I think everybody's worried and panickyAnd what are you working on right now? SoI'm a immunologist and also Oxford

Director of this new Institute ThisInstitute would prioritise the funding tosupport project including my own project,for example in terms of immunologystudying the immune response in patients,who is doing well and not doing well andthis is largely in collaboration withour colleagues in China, Beijing UNHospital and the Chinese Academy MedicalScience because they have collectedpatient samples from differentoutcome with different order which

Enable us to study the immune responseproperly Can I ask how you collaboratewith colleagues in China if China's onlockdown?I mean do you send samples through the post? Oh this is a long-term collaboration We startedour collaboration in 2002 so we've beenworking together on different virus anddifferent outbreaks, like HIV Sars timeand avian flu One of the the reason we won'thave this joint institute is we canreact very fast when something like this

Happened and it's not just matter forthe locally It's a global problem andit needs a global effort to really join force and combine the strengths,sharing the resources, reagent and theknowledge and expertise to fight asquick as we canTao's team are already set up to fightevents just like the Covid-19 diseaseoutbreak As humans increasingly encroachon animals' territory, they're unwittinglymeeting millions of tiny microbial

Organisms living inside those animalsSome of which could infect usSo scientists figured this disease orsomething like it has been coming for a whileOne thing Tao mentioned therea moment ago werereagents and the importance of sharing themWhat's a reagent?This is a really fantastic work Chinese scientists havedone is they published a sequence, virus

Sequence, very, very quickly That means wecan just by looking at the sequence wecan synthesise So now just by havingthat sequence we can make the protein in two weeksWhat is the protein? You're not building the virus again?Spike protein, because that'simportant immunity for making antibodiesfor vaccines Spike protein is veryimmunogenic and this is outside of the virusSo it's quite important I shouldsay to our listeners that Tao is kind of

Making her hands into a ball in the airI feel like you're trying to describethe virus if it were a ball Can you giveme a description of what coronavirus looks like?You have a like a ballinside, then you have all this, what is itcalled, it's very hard to do them, justthinking about Okay so you know in mydaughter's school some boys have thisvery gelled hair Spikey hair It's a bit like thatSinging star you know It just points tolike different directions but it's quite

Distinct so that's why you want to make a kind of antibody They can bind to it and they can stop itYou're listening to CrowdScience from the BBC World ServiceIt's time for us to head into the lab wherescientists will be unpicking the virusto work out how it gets into our bodiesand cells and how it interacts with ourimmune systemDon't touch anything! We won't We're here answering listener Evelyn from Colorado's question

What can scientists do to combat Covid-19 disease?Coronavirus isn't the only virus Tao andher team are working onIit turns outthat from a scientific perspective thereare some similarities between coronavirusand another well-known virus – HIVWe learnt a lot from HIV immunologystudy and lots of techniques we'vedeveloped is actually from HIVresearch for example isabella is a worldexpert in one technique it's called flow

Cytometry hello my name is Dr IsabellaPedrosa I am a senior scientist workingat the NDMRB We focus on vaccinedevelopment especially in the context of HIV infectionSo the experiment Isabellais very good at is one of the keyexperiments we want to do with thepatient samples Hopefully she will showyou with the machine and how the machineworks This place was built six years agoand appears to be everything you'd hopefor in a lab tackling some of the

World's most challenging diseases Whitebenches, computers, glass walls, all very high techAs we head towards a separateroom where Isabella's kit lives, a bluegloved scientist dashes towards the doorSorry we'll be like twominutesScience gets priority and this machineis in high demand Once the files aretransferred Isabella guides us in to seethe flow cytometer

This is a flow cytometer As you can see this is amachine that is around 1 meter times 1 meterThe flow cytometer and immunologyplays a very, very important role in researchThis is a machine that allowsthem to look at the physical andchemical properties of cells The teamwill use this to try and work out whytwo patients with the same coronaviruscan react in very different waysWe can tease out the differences in the immunesystem of each individual and compare it

Between populations as well and we cananalyse millions of cells at onceSo the flow cytometer plays a verycritical role in terms of vaccination strategiesWe're in the process ofgetting some samples here so will happen soonCurrently this machine is being usedfor other viruses but as soon as you'vegot the blood samples No we're probably not going to use this machine We have tohave a very safe environment which isapproved so it will happen in

Category three schedule 5 roomDesignated for Covid-19Category three means I'd have to put lab coats and facemasks Oh yeah, time to leave the lab viaa good scrub just in caseBack in Tao's office I wanted to knowhow Covid-19 patients' immune systemsare responding to the diseaseResearch into this topic is really early days butfrom what's already out in theliterature, Tao's particularly interestedin a reaction seen in some patients

Called a cytokine storm To fight off aninfection our immune cells need tocoordinate their attack They do thisusing a set of proteins as chemicalmessengers These proteins calledcytokines give the immune cells theirinstructions They're also responsiblefor the reactions fever, aches, runny nosethat you know of as symptoms of manycolds and flus Now, occasionally severeinfections set up this disastrouspositive feedback loop, producing way too

Many cytokines and creating a hugereaction It's thought that cytokinestorm caused many of the deaths duringthe Spanish flu epidemic of 1918So we set up some experiment already whichdo not need patient samples but we cantest to see how low cytokine mightregulate this response When you say thatit's the overreaction that causes damageto the tissue, is that what is causing deaths?We don't know yet but as I think thisis one of the possibilities based on

The patterns in how patients progressSo that's the team at the Chinese Academy ofMedical Sciences Oxford Institute tryingto understand the virus and our responseto it better but I'd rather not get itin the first placeWhat are scientists doing to protect usfrom Covid-19? For answers we head overto another Institute nearbyThis is Edward Jenner A statue of the father ofvaccination stands outside the Jenner Institute

Our guide here is SarahGilbert Professor of vaccinology She isa very busy woman and she's not the onlyone This department is on the front-lineof the effort to develop a coronavirusvaccine We're all quite sleep-deprivedWe've been working around the clock andthrough the weekend We're having to planmultiple things in parallel so it's it'san exciting time but it's also very stressful timeSarah and colleagues werealso working on vaccines for Mers, Lassa fever

And a hemorrhagic fever All workthat's been put on hold as they focus onthis latest threat They've also beenworking on speeding up the vaccinedevelopment process and that would bereally useful in this case So what is itabout the coronavirus that pushes it tothe top of the priority list?Well we know it's something that is spreadingvery rapidly now and we are going toneed to have a vaccine against it Whateverybody's now expecting is that even

If it is contained it's quite likely tocome back because it's spread so widelynow and it may not be contained It maybe something that goes through thepopulation and becomes part of the panelof viruses that causes respiratoryinfections every winterNow the Jenner Institute named afterEdward Jenner who basically did thefirst vaccine by taking cow pox andinoculating a child with it and theydidn't get smallpox

How has vaccine technology moved onsince then? It's moved on a long way butalthough there are still concepts inwhat Edward Jenner did that we use todayHe used one infectiousdisease to protect against another oneThe vaccines that we use are based on isan adenovirus vaccine An adenovirus iscaused by cold-like disease as well butwhat we've done is taken an adenovirusand removed some of its genes so that'snow very safe to use so it doesn't give

Anybody a cold, to which we can add thegenes from other disease-causingorganisms like the coronavirus Nowthings have moved on though and there'ssome slightly higher tech ways ofapproaching the vaccine Can you tell meabout how you build a vaccine? Well whatwe do is use molecular biology initiallySo we have the genome of the adenovirusWe have that in the freezer in the laband we've added some extra sequences toit so that we can then make more copies

Of it in bacteria and then we can purifythat DNA and we can manipulate it to addin a gene that encodes part of the novelcoronavirus for example that we want touse to make the vaccine and then we putthat into mammalian cells and thatstarts to form the adenovirus vectorsvaccine It can only make more copies ofitself in that particular cell line Soit doesn't do that when we use it as avaccine but that's the process that weuse to increase the amount of virus that

We have and then we have to purify thevirus away from the cells that we'veused to produce it on So we end up witha very highly purified preparation ofthe adenovirus with the novelcoronavirus gene in it and that is thenessentially the vaccine How long does ittake to make a vaccine? In the past it'staken anything up to 20 years From thepoint at which somebody decides to startmaking a vaccine to having somethingthat's licensed That means that it's

Ready to be used on a wide scale We areaccelerating a lot now but the worlddoesn't have a good track record onmaking vaccines for use against outbreak diseasesAs well as a plethora ofpractical problems there are ethicalquestions with trialling this kind ofvaccine Any good scientific trial has acontrol group – people who are given adummy placebo vaccine without anypotentially protective ingredient Is itfair to do that in an outbreak situation?

It's aquandary that Sarah's teams and othersdeveloping vaccines around the world arecurrently considering The other barrier is costHow expensive might it be todevelop this? Well it depends what youmean by expensive and if we compare itto what's been wiped off the stockmarket it's an absolute bargainObviously the money isn't there upfrontand that's the difficulty and the moneyis needed now to get these projects up

And running because you know if we sitaround and discuss it and decide what weshould do it's too late We started inJanuary as soon as the sequence of thecoronavirus was released, we've startedto make our vaccine So what is the timescale?When are you going to have avaccine developed?It's really very difficult to say for a number of reasonsOne reason is that we would normally dovaccine development in stages and we'dcomplete the first stage before we moved

On to the next stage and so we knowhaving completed manufacturing forexample we know we've got a vaccine inthe freezer ready to do the clinicaltrial with and we might run intoproblems with manufacturing So all ofthese things have to feed into theplanning together and we're trying towork out multiple things in parallel butwe're going to face problems withpossibly staff shortages because as theoutbreak spreads in the UK we might find

That people are isolated at home for awhile so that could hold us up we'retrying to do some planning around whatto do about that and it also mightaffect the supply of the raw materialsthat we need With each week we'regetting a bit closer to seeing where wemight be but at anytime something couldstop us and as the outbreak spreads Ithink it's going to be increasinglydifficult to do this kind of research So12 to 18 months? Those are the figures

That people have been saying We don'tknow It's not going to be extremely fastWe'll have to see how things happen tobe honest As soon as one person hastested a vaccine and shown that it worksit will help everybody else So very, verydifficult to predictSo preventative vaccines are going totake a while Almost certainly nothing intime to protect most people against thecurrent outbreak if it peaks in the nextfew months before dying down Before then

There might be something else to helppeople whowere already infected I said we'd returnto Peter Horby He's trialing drugscalled antiviral treatments There arenot many antivirals but there are anumber of existing medicines that areused for other purposes that in thelaboratory in the test tube have anantiviral effect and we're looking atthese and we have developed trials totry and see if they are safe which is

Very important in patients and also theyhave any effect either shorteningduration of illness or decreasing thelikelihood of getting complicationsHow do they work? Some of them interferewith the binding of the virus to thecells so it doesn't get into the cellwhere it replicates itselfSome of them interfere with some of theprocesses in the replication of thevirus so they all have differentmechanisms of action We've been working

With colleagues in China since the 2ndof January on testing quite a well useddrug for HIV actually so it targets aparticular enzyme which also you knowsimilar in the coronavirus So we'vebeen testing that in China to see if ithas any effect That's quite clever ifyou're testing something that's alreadybeing used for another virus then youknow it's toxicity levels and there'sit's not like starting off with a drugthat's entirely cold Yeah that's exactly

Right There's two classes of drugs thatwe could try One is what we callrepurposed drugs, so drugs that arealready licensed for other indicationslike HIV There's also drugs that areused for high blood pressure that mightwork so they're the ones that we'reprioritizing first to try and testThe other class of drugs is what we call theinvestigational drugs ones that are notcurrently licensed for any illness andthey're much higher the test because you

Need to get a better understanding ofthe safety etc How long does it take tofind out whether one of these antiviraloptions might work? The answer is don't knowWe have to get enough patients inthe trials they have to be what we calladequately powered which is enoughpatients in the trials to be able todetect a difference that's clinicallyimportant So you're usually talking youknow hundreds if not thousands ofpatients It can happen quickly or slowly

So at the start of the epidemic in Chinawe were recruitingyou know 20 to 30 patients a day and nowit's down to you know a handful eachweek and then you have to wait for thepatients to finish their period in thetrials so often trials will say assessthe patient finally at 90 days afterthey've received a drug to see what theoutcome is We want to go a bit quickerthan that so in our trials we've beenlooking at 28 days or even down to 14

Days but that still means you can'tdecide if a patient has recovered or notuntil the very last patient has reachedsay their day 28 which means you have atleast a month after the last patients inthe trial before you can report the resultsWhich do you reckon is going tocome first? A decent antiviral or a decent vaccine?Well we have the resultsof the antiviral trials before we'llhave the results of the vaccine trialsI'm sure but it's I don't have the guess

To whether any of them will work or notMost trials have a negative result youknow most things aren't as effective aswe would hope they are if the outcome ispositive when might people who becomesick be prescribed one of those drugsYou're probably talking to yeah anothercouple of months at least I think beforeyou'll have a really concrete result inany of the trials that might say thisdrug you know is effective and it couldbe used I think that's quite soon what's the catch?

Oh no it is quite soon youknow as I said most drug trust takeyears and years and years well the catchis is that the most likely result isthat these things don't have much of aneffect at all because with viruses youknow most people get a mild illness andso they don't need any treatment andthey don't come to hospital The patientsthat come to hospital they're oftenquite sick and what we've seen with thecoronavirus is that those patients that

Come to hospital are often quite late indisease and it may be quite unwell atwhich point treating them with anantiviral may not have a huge effectbecause they've already got a lot ofinflammation in the lungs etcSo you're trying to get a sweet spot for yourtrials where you're trying to prove thatthese antivirals are effective butthere's only a point early on inpeople's infections when it can reallyhave an impact? Yes and we call that the

Therapeutic window It's thewindow where you think an antiviral canhave an effect If you've got drugs thatmight work and you've got an at-riskpopulation why didn't just prescribethem anyway? It's very tempting to dothat but in the long run itscounterproductive because you reallyneed to be treating patients based ongood evidence that you're giving them adrug that is both safe and has thepositive effect Otherwise you end up in

This never-ending cycle of giving thedrug because you used to give it peopleexpect it It's very hard to stop thatpractice and it's very hard to do anyfuture research of new drugs becauseyou're then comparing it to an unprovenstandard of care Is this outbreak justgoing to be something that every countryin the world has to go through? I thinkit's quite likely yes It seems that it'svery infectious and that if you put inplace very stringent measures like has

Been done in China you can control theoutbreak but I think that's probablyonly temporary and the expectation is isthat in China once the control measuresrelaxed which inevitably they'll have tobe, because you can't stop peopletraveling or working etc, then there'llbe a resurgence of cases So I think it'sinevitable that every country willsuffer to some extent at least in theinitial phases It may be that in futureoutbreaks in future years and what we

See is that this becomes a more normalmild respiratory illness but becauseit's the first time that the population'sseeing this virus we're seeing moresevere disease this time around So it'snot gonna go away? My personal view isit's not gonna go away, no Petermentioned the results of one of hisantiviral trials are coming any day nowHead to this show's web page atBBCWorldServicecom/CrowdScience wherethere'll be a link to the published research

Once we get it So an antiviraldrug to lessen the impact of the virusmight be with us in a couple of monthsFrom what Professor Sarah Gilbert issaying a vaccine could be a year downthe line but really there are so manyunknowns that she's unwilling to put atimescale on it What I've taken awayfrom visiting all of these teams istheir sheer dedicationto the task in hand So thanksscientists The team that brings you

CrowdScience also make Health Check andScience in Action so if you do end upconfined to quarters keep downloadingthose podcasts from the BBC World ServiceThat's it for this edition ofCrowdScience from the BBC World ServiceToday's question was from me Evelyn inColorado USA The presenter was MarnieChesterton and the producer was JenWhyntie If you have a question thatscience might be able to answer pleasesend it to CrowdScience at BBCcouk

Thanks for listening Bye!you

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