3 Researchers Break Down COVID-19 Vaccines They're Developing

Dr. Seema Yasmin talks to three Covid-19 vaccine researchers who are developing three different types of vaccines.

Traditionally, vaccines are created by using a weakened or dead version of the virus and injecting that into the body.

Many of these developing coronavirus vaccines are using new technologies.

What's the difference between recombinant protein-based vaccine, a DNA-based vaccine and an mRNA-based vaccine?

- I called up threevaccine researchers workingon three different types of vaccines.Thank you so much for joining us,especially given how busyyou must be right now.- All right.- So, the traditional waythat vaccines have been madeis to inject either aweakend or dead versionof the virus into the bodyso that the immune systemis prepared to fight the real thing.But, many of the COVID-19vaccines currentlyin development are using new technology.- Hello, my name is Doctor Peter Hotez,and our team was developing arecombinant protein vaccine.- My name is Joseph Kim.Inovio is working on a DNAbased vaccine for COVID-19.- My name is KatherinJabsen, and we are working onmRNA vaccine candidates toprotect against COVID-19[solemn music]- There are over 30 companies workingon different types of vaccines,and these three researchers are allat different stages of the timeline.- We're now in the processof preparing our applicationto get the green lightto begin clinical trials,- Inovio is currently conductinga phase one studies for its vaccine.- We are currently ina phase one two trialin the United States and in Germanyevaluating for vaccine candidates.- Coronaviruses are RNA viruses,but your vaccine is a DNAvaccine, so how does that work?- Inovio's DNA vaccineswork by injecting snippetsof DNA as a vaccine intothe person's skin cells.The DNA, once delivered,instruct the cellsto manufacture the antigensencoded by the DNA.And then, once these antigensare produced in the body,the immune system of the personreacts to it by generating strong immuneresponses against those antigens.- An antigen is a moleculethat's foreign to your bodyand can elicit an immune response.DNA and RNA vaccines, insteadof giving you the virus,they're giving you some geneticcode that your own cellscan use to make a smallpiece of the virus.That's what your immunesystem is exposed to,and that's what it knows how to fight.- The beauty of thisis a safe way to teachthe immune system what thereal intruder would look like.So, mRNA is coding to make proteins.Our cells are loaded up with mRNAsthat are coding formany different proteinsthat are required in a human cell to dowhat the cell needs to do.- DNA codes for RNA, RNAcontains the instructionsto make proteins, and proteinsare the basic building blocksfor many parts of our body.- So, we taking advantage of this,of making a specific mRNAthat now is not codingfor cellular protein,but it's actually codingfor a viral protein.- Compare this to a protein based vaccine.- A recombinant proteinvaccine contains piecesof the pathogen that we'rehoping to protect against.- Can you define therecombinant protein vaccinethat your team's working on?- You're basically immunizingwith a piece of the virus,and that piece is geneticallyengineered into yeast.The way our vaccineworks is we formulate itwith something called alumto make it more immunogenic,and then you inject it, andit elicits an immune responseconsisting of antibody and also T cells.- How is a protein vaccine differentto an RNA or a DNA vaccine?- Well, a protein togetherwith the aluminum,what's called adjuvant,has the ability to directlystimulate the production of antibodies.That's in contrast toan RNA or DNA vaccinewhereby the RNA or DNA hasto be taken up by a cell.And then, one of your own host cellshas to manufacture parts of the protein,and then presented to the immune response.So it's two or threedegrees of separation awayfrom directly presentingto the immune system.The advantages of our vaccine,it says that old established technologythat we know can make a vaccine.RNA and DNA vaccines, they've never ledto the licensure of a vaccine before.The advantage of the RNA and DNA approachis you can make them pretty quicklyand accelerate the timeframe.- Most COVID-19 vaccinedevelopment started backin early January when Chinese scientistsfirst shared the geneticsequence for this new viruswith scientists around the world.- We were working on aseasonal influenza vaccinebased on mRNA when the pandemiccame upon us fast and furiously.when the Chinese madethe sequence availableof SARS CoV-2, our partners at BioNTechs,they took the sequenceand immediately startedto make COVID-19 specific mRNA constructs.- we were able to designa vaccine sequencein three hours by applyingthe known DNA sequenceof the virus, which wasavailable from China,leveraging what we knowof the coronaviruses,and what targets are appropriateas a vaccine targets.We were able to hone in andextract out the DNA sequencefor the spike protein, andthen turn that sequenceinto a very well optimizedvaccine sequence.- Both of these nucleicacid vaccine companiesbuilt their vaccines from scratchonce they downloaded the genetic sequencefor this new virus.Doctor Hotez's team hada different reactionwhen they saw the genetic sequence.- I'll never forget it.When they put their data up on bioRxiv,and I downloaded and said, "Holy crap."We may have a vaccinethat could cross protect."We've been working on coronavirus vaccinessince 2011 for nine years.- The team at Baylor College realizedthat they might have avaccine in their freezerthat would work againstthis new coronavirus.- Maria Elena, my science co-partner,had the vision to keepit on stability protocol.Meaning that in case peopledid get interested in it,when you put a vaccine on stability,it's taken out of thefreezer every six monthsand confirmed that it hasn'tbeen corrupted or degraded.What we had was, we had thegenetic code of the virus.Most importantly, since wewere focused on a componentof that spike protein calledthe receptor binding domain,you know, if you look ata picture of COVID-19,it looks like a donut with apiece of RNA stuffed inside,and then emanating out of thedome are all those spikes,and the rounded end of those spikesis the receptor binding domainthat docks with the receptor.We saw that there wasquite a bit of similarity.It was not a perfect match,but close enough that we thoughtthat our vaccine could cross protect.- Vaccine research beginswith preclinical trials on animals.What animals have you beentesting your vaccine in?- We've been testing ourvaccines in two types of mice.One is a genetically modified micethat makes the human ACE2 receptor.The other mice that are infectedwith moss adapted virus.- Vaccine candidates starts in mice,'cause they are very easy to deal with.- Mice are easy to come by.You can test many, manydifferent constructs in a mouse.It's a pre-screen.And so, a lot ofconstructs went into mice.Four came up on top,they gave good responses.T cell responses expect a Tcell humoral B-cell responsesto make antibody and DNA responses.- Typically, preclinicaltrials take years,as we heard from Doctor Hotez.But right now, thesecompanies are getting throughpreclinical trials remarkably fast.And how is it that you were able to startpreclinical development on day one?- We just did it faster and in parallel.We started the mouse testingsame time as the Guinea pigs,almost the same time as the rabbits,almost the same time asthe nonhuman primates.These are usually done in a serial steps.We just did everything in parallel.- Everything happens in parallel,but we are in a veryunique situation right nowin such an emergency.The question was, can we make a decisionin a mouse across those four constructs?And the answer was no,because mice ain't men,so we have to learn what would give usthe most potent vaccine construct.Actually, we made the decisionto move this into clinical studies.- This is often being pitchedas a race between vaccines,and I don't see it that way.I think you're gonna probablysee multiple vaccines emerge.- Once researchers are satisfiedwith the immune responsethat they're seeing inpreclinical testing,then they move on to human testing.[intense music]How far into clinical trials are you,and what's that process been like?- We just started a phaseone trial beginning of Aprilwith the first volunteer being dosed.All 40 volunteersreceived their first dose.- We have developed aphase one two programthat is really also a unicorn.Very unique, because it iswhat we call a seamless trial.It starts with a smallgroup of individualsthat will receive the four candidates.We then will make very quick,real life decisions basedon the emerging data of whichcandidates will move ahead,and which candidates will be eliminated.- Pfizer is doing phases one and twoof its clinical trials at the same time.Many companies are doinga lot more in parallelthan would normally happen.What all of these vaccinescientists are looking foris the right kind of immune response.What kind of immune responsedid you see with your vaccine?- We were able to see very strong,robust antibody and Tcell immune responsesagainst our vaccine antigen.- The immune response that our vaccineis inducing is actually ableto prevent the infectionor at least the diseasein the animals that isto induce a responsethat we call an innate immune response.So, that's usually immune responsethat recognizes dangerous signals,like there's a virus coming in,or there's a bacterium coming in.While this is happening,the RNA is also inducingwhat we call adaptive immune responses.So, here we get T cell responses,both T cells that give help to other partsof the immune system, but alsoT cells that by themselvescan recognize virally infected cellsand kill those cells toeradicate the infection.So, that was also very important.This is what we call the humoral partof the immune responsesso that's immune responsethat produces protective antibodies.We like the RNA, because all three armsof the immune system aretriggered at the same time.- Can you walk me through how your vaccinewould work in somebody's body?- The immune system sees these geneticallyengineered antigens andproduces an antibody,and the antibody binds to thespike protein of the virus,then shuts the virus down.- Once a vaccine makes it through testing,the next major challenge is storage,and the stability of a vaccinecan make it or break it.How does a protein vaccine comparedto RNA/DNA vaccines in terms of stability,and what temperature you have to keep at?- DNA vaccines, another advantage is,you don't need to keep it cold.Our vaccine, you need to keep cold.- DNA plasmids is one of the most stablebiological molecules in the world.We've demonstrated our longterm storageis at normal refrigeration temperature.We can make it set downin room temperaturefor over a year with perfect stability.- Our vaccine candidatesright now are stored frozen.The stability of RNA, there'sstill some work to do.In order to get the RNA into the cell,it needs to be formulated forlack of a better description,in a little fat droplet.So, there are lipids involved.They surround the RNA, theyhelp stabilize the RNA,and so this little fat dropletthen serves as a vehicleto be taken up by a human cell.- Once the vaccine's madeit through clinical trialsand safety testing, the next big stepis scaling up and manufacturing.- I think the way the approach nationallyhas been to try to get lots of vaccinesaccelerated into clinical trials.So, you get lots of shots on goal,and then you have thisinteresting phenomenonof manufacturing at risk.That's the term Doctor Fauci uses,which is manufacturingthese vaccines in scale,even though you don't know it'sgonna work or if it's safe.- We've been thinking aboutscaling up our manufacturingof these vaccines from day one.You know, if we're successfulwith COVID-19 vaccine,we need to manufacturebillion doses a year, right?Potentially, at least hundredsof millions of doses a year.So, that's a scale that we were notpreviously built to handle.Thankfully, there are a lot of folkswho have committed bothfrom the government levelsand the NGO levels tosupport the scale up.- We have this, of course in mind,and already working onthe scale up activitiesto at least produce hundredsof millions of doses.- The question on everyone's mind,when will we have a vaccine?- If everything goes well,and if the emergency use pathis available,, potentiallyby the end of this year.- I don't see a path by which you're goingto have a vaccine available by the fall.I don't see how it's possibleto collect sufficient datato show one, the vaccine works,and second that the vaccine is safe.- In our situation, we don't have years,we don't have months, time is up.We need to be really, really fast.What took years we now do in months.In my wildest dreams,I would have never evenimagined that this is possible.- This acceleratedtimeline for developmentof a COVID-19 vaccine is unprecedented.We have never seenvaccine development happenat this rate with somany different candidatesall being tested to fight the same virus.We're seeing cutting edge,never before approvedtechnologies being triedand tested alongside muchmore traditional methods.There are so many different kindsof vaccines being developed right now,so I hope this brings some clarityabout the different methodsthat are being used.Check out my other video,which explains just how soonwe might have a vaccine.Thank you so much for taking time outof your busy schedule to talk with me.- Thank you very much.It was a pleasure talking to y'all.- No problem at all.- All the best, bye bye.