– I called up three vaccine researchers workingon three different types of vaccines. Thank you so much for joining us,especially given how busy you must be right now. – All right. – So, the traditional way that vaccines have been madeis to inject either a weakend or dead versionof the virus into the body so that the immune systemis prepared to fight the real thing. But, many of the COVID-19 vaccines currentlyin development are using new technology. – Hello, my name is Doctor Peter Hotez,and our team was developing a recombinant protein vaccine. – My name is Joseph Kim. Inovio is working on a DNA based vaccine for COVID-19. – My name is Katherin Jabsen, and we are working onmRNA vaccine candidates to protect against COVID-19 – 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 process of preparing our applicationto get the green light to begin clinical trials,- Inovio is currently conductinga phase one studies for its vaccine. – We are currently in a phase one two trialin the United States and in Germanyevaluating four vaccine candidates. – Coronaviruses are RNA viruses,but your vaccine is a DNA vaccine, so how does that work?- Inovio’s DNA vaccines work by injecting snippetsof DNA as a vaccine into the person’s skin cells. The DNA, once delivered, instruct the cellsto manufacture the antigens encoded by the DNA. And then, once these antigens are produced in the body,the immune system of the personreacts to it by generating strong immuneresponses against those antigens. – An antigen is a molecule that’s foreign to your bodyand can elicit an immune response. DNA and RNA vaccines, instead of giving you the virus,they’re giving you some genetic code that your own cellscan use to make a small piece of the virus. That’s what your immune system is exposed to,and that’s what it knows how to fight. – The beauty of this is a safe way to teachthe immune system what the real intruder would look like. So, mRNA is coding to make proteins. Our cells are loaded up with mRNAsthat are coding for many different proteinsthat are required in a human cell to dowhat the cell needs to do. – DNA codes for RNA, RNA contains the instructionsto make proteins, and proteins are the basic building blocksfor many parts of our body. – So, we taking advantage of this,of making a specific mRNA that now is not codingfor cellular protein, but it’s actually codingfor a viral protein. – Compare this to a protein based vaccine. – A recombinant protein vaccine contains piecesof the pathogen that we’re hoping to protect against. – Can you define the recombinant protein vaccinethat your team’s working on?- You’re basically immunizing with a piece of the virus,and that piece is genetically engineered into yeast. The way our vaccine works is we formulate itwith something called alum to make it more immunogenic,and then you inject it, and it 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 together with the aluminum,what’s called adjuvant,has the ability to directlystimulate the production of antibodies. That’s in contrast to an RNA or DNA vaccinewhereby the RNA or DNA has to 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 three degrees of separation awayfrom directly presenting to 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 vaccine development started backin early January when Chinese scientistsfirst shared the genetic sequence for this new viruswith scientists around the world. – We were working on a seasonal influenza vaccinebased on mRNA when the pandemiccame upon us fast and furiously. when the Chinese made the sequence availableof SARS CoV-2, our partners at BioNTechs,they took the sequence and immediately startedto make COVID-19 specific mRNA constructs. – we were able to design a vaccine sequencein three hours by applying the known DNA sequenceof the virus, which was available from China,leveraging what we know of the coronaviruses,and what targets are appropriate as a vaccine targets. We were able to hone in and extract out the DNA sequencefor the spike protein, and then turn that sequenceinto a very well optimized vaccine sequence. – Both of these nucleic acid vaccine companiesbuilt their vaccines from scratchonce they downloaded the genetic sequencefor this new virus. Doctor Hotez’s team had a 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 vaccine that could cross protect. “We’ve been working on coronavirus vaccinessince 2011 for nine years. – The team at Baylor College realizedthat they might have a vaccine in their freezerthat would work against this new coronavirus. – Maria Elena, my science co-partner,had the vision to keep it on stability protocol. Meaning that in case people did get interested in it,when you put a vaccine on stability,it’s taken out of the freezer every six monthsand confirmed that it hasn’t been corrupted or degraded. What we had was, we had the genetic code of the virus. Most importantly, since we were focused on a componentof that spike protein called the receptor binding domain,you know, if you look at a picture of COVID-19,it looks like a donut with a piece of RNA stuffed inside,and then emanating out of the dome are all those spikes,and the rounded end of those spikesis the receptor binding domain that docks with the receptor. We saw that there was quite 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 been testing your vaccine in?- We’ve been testing our vaccines in two types of mice. One is a genetically modified micethat makes the human ACE2 receptor. The other mice that are infected with 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, many different constructs in a mouse. It’s a pre-screen. And so, a lot of constructs went into mice. Four came up on top, they gave good responses. T cell responses expect a T cell humoral B-cell responsesto make antibody and DNA responses. – Typically, preclinical trials take years,as we heard from Doctor Hotez. But right now, these companies 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 testing same time as the Guinea pigs,almost the same time as the rabbits,almost the same time as the 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 very unique 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 pitched as a race between vaccines,and I don’t see it that way. I think you’re gonna probably see multiple vaccines emerge. – Once researchers are satisfied with the immune responsethat they’re seeing in preclinical testing,then they move on to human testing. How far into clinical trials are you,and what’s that process been like?- We just started a phase one trial beginning of Aprilwith the first volunteer being dosed. All 40 volunteers received their first dose. – We have developed a phase one two programthat is really also a unicorn. Very unique, because it is what we call a seamless trial. It starts with a small group of individualsthat will receive the four candidates. We then will make very quick, real life decisions basedon the emerging data of which candidates 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 doing a lot more in parallelthan would normally happen. What all of these vaccine scientists are looking foris the right kind of immune response. What kind of immune response did you see with your vaccine?- We were able to see very strong,robust antibody and T cell immune responsesagainst our vaccine antigen. – The immune response that our vaccineis inducing is actually ableto prevent the infection or at least the diseasein the animals that is to 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 also T cells that by themselvescan recognize virally infected cellsand kill those cells to eradicate the infection. So, that was also very important. This is what we call the humoral partof the immune responses so that’s immune responsethat produces protective antibodies. We like the RNA, because all three armsof the immune system are triggered at the same time. – Can you walk me through how your vaccinewould work in somebody’s body?- The immune system sees these geneticallyengineered antigens and produces an antibody,and the antibody binds to the spike 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 vaccine can 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 down in room temperaturefor over a year with perfect stability. – Our vaccine candidates right now are stored frozen. The stability of RNA, there’s still some work to do. In order to get the RNA into the cell,it needs to be formulated for lack of a better description,in a little fat droplet. So, there are lipids involved. They surround the RNA, they help stabilize the RNA,and so this little fat droplet then serves as a vehicleto be taken up by a human cell. – Once the vaccine’s made it 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 this interesting phenomenonof manufacturing at risk. That’s the term Doctor Fauci uses,which is manufacturing these vaccines in scale,even though you don’t know it’s gonna work or if it’s safe. – We’ve been thinking about scaling up our manufacturingof these vaccines from day one. You know, if we’re successful with COVID-19 vaccine,we need to manufacture billion doses a year, right?Potentially, at least hundreds of 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 both from the government levelsand the NGO levels to support the scale up. – We have this, of course in mind,and already working on the scale up activitiesto at least produce hundreds of 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,, potentially by 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 possible to 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 even imagined that this is possible. – This accelerated timeline for developmentof a COVID-19 vaccine is unprecedented. We have never seen vaccine development happenat this rate with so many different candidatesall being tested to fight the same virus. We’re seeing cutting edge,never before approved technologies being triedand tested alongside much more traditional methods. There are so many different kindsof vaccines being developed right now,so I hope this brings some clarityabout the different methods that are being used. Check out my other video,which explains just how soon we 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.