COVID-19 Chapter 5: Vaccines

We are both experiencing shortness of breath, chess congestion, cough, mild fever, and general body ache. Our case manager with the public Health Department spent most of the afternoon fighting to get test ordered for us. When we called urgent care to say we were coming, they told us to stay home. They agreed to see us when we explained that the Health department told us to get tested at

our nearest urgent care. The Washington Post is reporting that sick people across the country are being denied coronavirus testing. If my husband had not been exposed to a confirmed case, I believe we also would have been denied. How will we know who has the sickness if testing is not widely available. Our urgent care appointment was incredibly frustrating. The

nurse met us at a side door with masks. We were there for nearly two hours, and no one seemed to know how to treat us, what protective gear they were supposed to wear, what questions to ask us. The nurse took off her face shield while in the room with us to make it easier to see the computer. We overheard her say she has pneumonia. Why was a

nurse with pneumonia assigned to us? We were there for nearly two hours, and the whole time could hear people outside of our room asking one another what to do. Someone was on the phone with what seemed to be the CDC. Their guidance appeared to change while we were there. The healthcare system is not prepared for a pandemic. We were first tested for flu. My results came back positive, my husband's negative. We were both written prescriptions for TAMA flu.

We were also tested for COVID nineteen, but will not hear back until Monday or Tuesday, and maybe even Wednesday because labs are not staying open over the weekend. When you get tested for COVID nineteen. You have to sign a form saying that, among other things, you will self quarantine until you get your results back. Our doctor sent our tamiflu prescriptions to a pharmacy inside of a target.

We had to point out to her that this would break our quarantine and maybe it would be a better idea to send it to the pharmacy that was literally next door and offer a drive through pickup. It still took over two more hours to fill our prescriptions there, as the one sent to target was not canceled properly. So now we wait under mandatory quarantine. We have enough food and other supplies, but worry for others who do not.

I hope the government and healthcare system figure out what to do and quickly.

your immune system responds to vaccines. So if you haven't heard it, or if you've forgotten entirely, which you know, I'm among those, it exists online for you. But for this interview, let's quickly go over some of the different types of vaccines. There are whole vaccines, so this is a vaccine that's made of an entire virus or bacteria, and those can either be killed or what we call attenuated, which means that they are less virulent and they can't

really cause disease. There are component vaccines, which means the vaccine is made of pieces of the virus or bacteria, usually components of their surface, so that our body can make antibodies against these surface proteins that can help then fight off the virus if we ever get exposed to it.

And finally, the newest kinds of vaccines, which I think are fascinating are DNA or RNA vaccines, and so that means injecting the DNA or RNA sequence or part of it, of the virus or bacteria into your muscle, and then your body has to use that sequence to make the proteins, and then your body makes animodies to those proteins, thus immunizing you.

But both of these types of vaccines take a long time to produce, largely because they require first isolation and then culture of the pathogen in question, and then you have to grow that pathogen in large enough quantities to be able to produce a vaccine, So that whole process takes a long time and a lot of money too.

to create a vaccine. But even though we can do this more rapidly than in the past, and even though genetic tools give us a kind of a head start on this, as you'll hear our guests explain, there are still very many steps to the development of an effective vaccine and they can't be skipped.

that process along while still maintaining safety standards. So the vaccine that her group is working on is a component vaccine, so it's made of that spike protein that you've probably heard a lot about in the news and if you've listened to the other episodes in this series. But we'll let her introduce herself and tell you all the details about the vaccine that she's working on right after this break.

with other I guess researchers. But at the same time, in the nonprofit sector, try to build these vaccine technologies with the ultimate mission that they can be affordable, reachable, and certainly be deployed to popular relations who really need them, you know, for the public good.

be successful at developing vaccines. And certainly now you even hear that most of vaccines are being developed in this new I guess era compared to maybe the old generation vaccines like you know, the measles, mumps, rubella. Is that new vaccines tend to becoming more and more that are not considered fully protective type of vaccines, but they are vaccines that are geared to reduce the severity of illness, maybe reduce the certain intensity of infections by different pathogens.

And it's getting harder and harder to develop vaccines that are going to one hundred percent protect an individual. But that's still okay, right, I mean that you know that

that's better than nothing. You know. Again, you know, I think the value of vaccines, whether they're fully protective or they are partially protected, ultimately is to try to again reduce deaths, reduce severity, hence reducing people to having to engage the healthcare systems by being hospital eyes or of course even going all the way to being put into intensive care units, and change the way that we therefore can manage these diseases by you know, being able to

treat them like if you were getting a common call with you can basically maintain them through some simple at home type of containment or even just clinical management.

Therefore we avoid also putting in any components of the pathogen that is really not necessary for us to confer protection in the human host, you know. So, yes, I mean the procedures, the ways that we produce vaccines, test vaccines, you know, have some level of impact of how quickly we can move them. But I think the second, which is the fact that pathogens, the ones that we consider the easy pathogen that we knew we could develop vaccines

very rapidly, most likely we already did them. But now we're dealing with very complex pathogen is that even have very multiple transmission modes or that their cycle of survival is you know, inclusive and an intermediary vector or reservoir. Right. So you know, I just can give you an example, you know, the malaria vaccine, right, Why has it been so hard? Because what do you develop a vaccine against?

Which stage of the parasite? You know, do you do it from the parasite that is in the blood stage or in the or or not do you look at you know, the parasite when it's inside the mosquito. These viruses, more and more are also quite intelligent in themselves, so they're very complex in the nature of how they not only find ways to infect but also where they come from.

And therefore it makes it a little bit more challenging for us to find how we can tackle them and prevent them to not only infect us, but certainly cause disease.

that use that same technology. So the backbone therefore of the way that we want to make the vaccine, it's proven and already has a lot of safety and as well as data on how you can rapidly produce it and how good are they by scaling them, and certainly even the amount of costs. You know that these types

of platforms costs. So recombin and protein based vaccines are in general quite affordable and more importantly, they don't need to have very sophisticated manufacturing plants, and even in low middle income countries that do have capacity to develop their

own vaccines could rapidly adopt them. That is certainly one consideration that we want is that you know, we don't develop something that is too much of a high cost or it has too much complexity in the technology that then we can only make it in the US and then nobody else is able to adopt it because it's just too expensive or too labor intensive. So that's one aspect.

The second aspect, specifically for COVID nineteen is that everybody is trying to attend and to develop a vaccine targeting what they call the spike protein, which is the protein the virus uses to infect the human cells. But even within the spike protein, there are a lot of components that maybe it's they're not necessarily useful in the induction

of this protective response. So we with a group of partners from the New York Blood Center as well as the University of Texas Medical Branch here in Galveston, we were kind of like picked apart the spike protein and we narrow down what we think it's the most essential piece that we need for us to be able to induce our response in humans that is protected but at the same time evaluates the safety of using it. So it's it's actually a small piece that it's called the

receptor binding domain. So amongst the spike protein, the like uses this domain to specifically target this component in our human cells that needs to be bound on and therefore used to be to infect the cells. So we therefore engineered in our lab a recombinant protein that specifically just expresses this receptor domain, and when you put it in the right formulation, we know that in animal models it does induce a strong and certainly efficacious response and protects

against a challenge of the SARS virus. Now there's a disclaimer here that you know, our vaccine was developed back in twenty eleven, so the engineering of this vaccine was really based on the SARS virus that was circulating at that time and not COVID nineteen virus. But there are several evidence and strong scientific evidence that the two viruses are very similar to each other. So we believe that we should evaluate it to see whether there may be a potential of cross protection.

on this small domain. We also are, in parallel trying to engineer a brand new vaccine that is against specifically the RBD of this new virus. But in the meantime, you know, since we are already so advanced with the prior vaccine, because we already even have it in our freezers, manufactured with a grade that can be used in the clinic, we think that we should not just wait for us to develop a new one. We should, you know, in parallel, start evaluating the one that we already have designed.

of the spike, so rapidly we clone that. We have to look for the process for making it at laboratory scales. But then that laboratory scale has to be scaled up to the point where it becomes not only a pilot scale in manufacturing agencies, but eventually even what we call industrial scales. That's just that sole process of from the cloning, engineering, to scaling and producing usually can take from six months all the way to maybe eighteen months to even twenty

four months. And of course it depends on is it easy to make it? Is it not easy to make it? Are the processes very complicated? Since we already know four stars that we already had developed was a very simple approach, and it ended up being quite an easy process. Instance, think that, you know, we could have a new process for the stars to RBD or the COVID nineteen RBD

in probably the next six months, so that's one piece. However, after that, of course, you know, producing something doesn't tell you whether it's usable, or if it's going to be safe, or if it's going to be protected. So we before going to humans, you have to start a whole pre clinical plan where you have to have an animal model of course, that has to be suitable for the pathogen that you want to test your vaccine against. We know that there are currently several groups that have been developing

these COVID nineteen animal models. They probably are not ready one hundred percent, but you know there are already a few that people are using to be able to evaluate any kind of vaccine or even even drugs for example. So that process of evaluating your produced vaccine candidate usually can take again another six maybe to another nine months, So there goes a year, right, and that's just only

pre clinical. After that, when you decide that yes you can make it, yes you have indication in some model, then is the critical activity start. And by critical activities mean what we call the regulated the activities that then you can provide as evidence to a regulatory body, in

our case the United States Food and Drug Administration. So that they can evaluate that information, and those include three main components, so a formal manufacturing campaign, a formal toxicology studying, an animal model, and then of course a plan of how you're going to do the first in human safety evaluation.

And those three activities generally take another year or a year and a half, so you already have one year for that what we call research and development, one year maybe two years for the initial critical path activities, and after you finish that first, then you design a long term plan where eventually you evaluate in larger populations, you look at efficacy, you look at safety, and so as you can see, it can be a two to three year program, or it can become a ten year, twenty year,

thirty year. As you have seen for many other vaccine programs, there is never an assurance that we will find one. But of course you have to do the studies to be able to evaluate if there's even the feasibility of doing.

you can stagger and maybe do things in parallel. So, for example, as you're already developing this process, you rapidly already engage the manufacturer and you could already have them do some what we call engineering runs, and therefore you don't have to wait until you have a process fully developed before you already engage a manufacturer, right, so you

condense it that way. In the area of pre clinical testing, you may be able to while you're doing some of these pre clinical tests, you already ramp up to have a design for your toxicology study. And then on top, as you're doing your toxicology you don't have to wait for the end of it while as if you release the safety data as it comes out, I guess educates

how you can then start your clinical study. So normally they like you to do one thing and then get all the data and review it and then plan for the next step. In these kinds of emergencies. They're allowing you that you can unblind some of the information so that you can start things in parallel and not necessarily wait until you have a study totally completed. And that's

how they're trying to condense the timelines. But definitely one thing that you cannot do is you cannot skip steps, right, I mean, I think even though maybe in the news there's this perception that, you know, how could have they

done this? You know, we haven't seen any data because ultimately, you know, we in the scientific community, we get access to the information because people publish it or make it available, right, I mean, right now, I think either there's been no time to sometimes see all the data that is kind of around, or sometimes we do see data, but it hasn't really been evaluated by peers. So it's at the same time, it's quite struggling, right because these agencies, I assume,

have purview of information that maybe not all of us have. Uh. And it's the key to have experts in whatever communities they're set up to make sure that they try to make the most safe and appropriate decision. And that said, you know, it's it's it's a strong, big pressure on people right to make these decisions when you on top have this urgency behind you, right.

healthy populations. So the risk benefit of giving something to a healthy person that eventually can then lead to something that is of high risk, the bar is a lot higher, right, you know, you're a little bit more cautious of what you use to give to a healthy person. Therapy is as you know, and they're intended to be therapeutics, and therefore you're already tackling and supposed to use them and

already sick people. So the bar it may be a little bit lower, right because being sick and being certainly severely sick, and with the option of death, you know, there's a lot of protocols that you can use with the argument of compassionate use, where you know you are trying to really evaluate that this is going to not only extend the life or certainly improve the quality of life in an event that you know you can, you know,

totally prevent the ultimate death. Right for now, as you can see the level of urgency as you've heard in the news. First, have the deal diagnostics right, because you need to know who is infectant and who's not. Second is, if you already have those infected, how can you really prevent these people to have severe disease and therefore avoid death. And so here is where a lot of therapies are being rapidly evaluated and even even repurpose some therapists that

may be used for something else. They are evaluating them. But ultimately, in the long term, you want to if you can't avoid infection, through the either containment or other practices. You eventually will need to have a preventive vaccine, right, because even if this outbreak or pandemic disappears, if there were to be something in the future, you don't want to scramble again just to try and to find therapies.

You want to have a full toolbox, right, good diagnostics, good preventive measures for those who haven't gotten the disease yet there and also already have therapy for those who are unfortunately do get it.

So that's definitely a distinction. I think the unpredictability, right, you know, that you cannot really predict, you know, even how these curves will be looking how you know, certainly what happened in China and what's happening in Europe. We're trying to make a lot of inferences of what's going

to happen maybe in the Americas. So there's a lot of unknowns and and I think it's it's the stress that everybody has, not only personally as an individual, but as a community, but you know, including all the first responders and certainly the medical and researchers that are you know,

more in the trenches about this. It's it's very hard to predict, right, So we should take this seriously and try to as Mutch we you know, are not very happy, you know, to try to really contain our social connectivity

at this point. And it's it's tough now, I think, you know, the other challenge that I see is and I appreciate that a lot of media is trying to push information is it's still you know, again to be very conscious of the quality of the information that is being pushed out and who who is using reputable sources, Where are the reputable sources to look at, and not get totally blindsided by the noise that it's really trying to disrupt, you know, where the real information is and

people are just getting distracted. So I hope that we can figure out a way and this is a lesson learn of the power, of course of media and social media, but that at the same time it's it's making our lives a little difficult because people are just getting distracted

by information that is just absolutely not useful. And then I think in the area of again developing vaccines, if anything, I hope that this just that the population understands that ultimately those of us who are working on these types of interventions, we don't take this lightly. That the way we do this is you know, to ensuring first and foremost the safety of anybody that will eventually use them, and so that they can reinvigorate again their their acceptance

that vaccines work. That even in the context of COVID nineteen, there are so many other diseases that are certainly potentially important.

There are a lot of them already have vaccines that clearly either one hundred percent protect or even partially protect, and we should therefore continuously ensure that we are up to date with our vaccinations because I think, you know, we're also seeing that there was a little bit of disconnect about you know, the value of vaccines and how it brings value as a public health tool, and that this is really a public health you know that all

communities have to engage and needs to support these types of initiatives.

and they're all doing this simultaneously. So there is a group that has started safety trials, so phase one trials of an RNA based vaccine, and I think this is pretty exciting because this is the first of its kind in humans that's actually being tested in humans. There are DNA based vaccines that are being used in animals right now, but this one, it's the first RNA based vaccine that I know of, and it's the first one being tested in humans. So it's going to be very interesting to

see how that trial goes. And if you want to know even more details about the work that doctor Botazi is doing, as well as what other types of vaccine trials are going on, remember that you can check clinicaltrials dot gov to see all of the registered human clinical trials for vaccines and drug treatments. So yeah, point two.

that we know nothing about. So we're starting from scratch in a lot of these cases, and that can make the creation of a successful vaccine much more challenging.

shorten the time course of vaccine development. So the fact that there were groups like doctor Batazzi's group already working on vaccines for similar viruses means that they already had platforms in place which could be built upon, and that's unbelievably helpful in trying to hasten the development of vaccines for novel pathogens.

of a particular vaccine versus a particular treatment. And this is interesting because honestly, we don't have a lot of specific treatments for most viruses, but we'll hopefully talk in a future episode about how many different treatments are out there that are already trying to help people currently infected with SARS CoV two.

potentially life saving treatments and vaccines. And so I think We've kind of touched on this in almost every episode, but funding science research is really important.

an issue. And so if you want to make an impact, if you want to spread the word, you can just spread it by talking about it, or you can contact your congress person if you're in the US, make your vote matter with these sorts of issues and topics, and so this is something that you can make an impact on and it you know, I kind of feel like we're just shouting into an echo chamber a little bit, but you know, let's get the message out there.