What is the outlook on the production of a COVID-19 vaccine?
I think it’s clear that there are many vaccines that are hopefully going to be evaluated soon, so the pipeline is pretty nice. ... It's good to have a robust pipeline, meaning we’re not just assuming that one [vaccine] is going to be the only one that’s going to be a solution for all. Vaccines certainly have a high rate of failure due to the nature of how you develop them and what the expectation of a vaccine [is], which of course is a preventative measure.
I think there’s optimism, and that’s why our call to action is that as many as possible should go into their evaluation stage ideally to the point where we can evaluate them in a first-in-human study. You can go crazy doing very complex and comprehensive preclinical animal studies that are research, but then we need to have them transition into the critical path, meaning the regulatory-enabling package of information that is really going to help regulatory bodies make that determination: Is there enough evidence that this vaccine in platform X delivered as Y is suitable for it to go into a human study?
How much is the testing phase expected to be sped up now?
Because it’s not business as usual, the regulatory bodies are evaluating how they can allow certain things to maybe be done in parallel rather than sequentially. ... It’s going to be very difficult to skip a step; I don’t think that’s really going to be able to be done, but at least steps can be shortened by sharing the information just in time even though there are risks. Because when you have time to look at the data and study it and interpret it with time, you can look at things with a different set of eyes rather than trying to rush things. Again, we’re not doing business as usual, so a lot of things may be done with a little bit higher level of risk ... with as much scientific evidence that justifies such a decision.
For those not familiar with the process, how are vaccines produced?
The first thing you need to do is identify what within the pathogen is important enough that you want to interfere with. If you look at the coronavirus, everyone is talking about interfering with the virus to be able to enter the human cells. And therefore we know that the element within the virus that is essential for this activity to happen is this ‘spike’ protein. So most of the vaccines are targeting [a] full-length spike or portions of the spike. We specifically believe that a very small domain of that spike protein [is] enough for us to build a vaccine. And then what you do is you replicate that protein. ... And so what happens is when your body sees this foreign protein, the body knows that it’s a foreign entity, and then we have an immune response. It kind of builds an army to destroy that protein. And that’s what we use as our means for us to combat these diseases. Because when you vaccinate, you’re vaccinating with something that resembles a very important piece of the pathogen. We build the army, meaning the antibodies or the cytokines or whatever the different immunological cells or products [are]. And then we then eventually get the virus; we remember that they’re a foreign entity, and we already have an army ready to respond.
What are the differences between developing a vaccine based on DNA or RNA versus a protein?
When you inject a DNA molecule into the body, that DNA somehow has to figure out how to get into some cell within your own individual cells. And you’re asking your own machinery to then do the production, to be the producer of the protein. ... And indeed maybe that’s one of the reasons why we still do not have an approved DNA vaccine. Because it’s not as easy to inject DNA and say, ‘Okay, human body ... figure out how to make it into a protein.’ And the same at some level goes for the RNA. You’re asking your body to go through steps. You’re asking your body to produce the proteins. With proteins, arguably you’re asking a little less from your body. You’re basically telling the body, 'Okay, here’s a protein; the only thing you guys have to do is figure out how to chop it all up and present it to the right system so we can make antibodies.’
The delivery of RNA and DNA [vaccines] and protein [vaccines], it’s probably very different. ... How do you package the RNA or the DNA? That’s also not been 100% figured out. That’s why both DNA and RNA vaccines are in different stages of experimental evaluation. While proteins, if anything, we pretty much already know how to deploy them. ... So it’s a little bit more complex because it’s the entire packaging.
What are the challenges of producing vaccines at a large scale?
The technology’s being developed by what we consider small biotech companies, and there is certainly no expectation that small biotechs are the end industrial manufacturer. Because usually that’s not what happens. ... For it to become real for world markets, you have to have the so-called industrial entities. So when you say, ‘Right now, who can make industrial levels?’ Nobody, because they don’t exist. ... Most likely they not only are going to have to build a brand-new infrastructure, but they have to bring in the right equipment, and they have to bring in the right personnel that know how to do this. Right now there's not many people that can do it at these large scales.
The industrial manufacturer also plays a role when you’re in development. The maturity of the process may be early or slightly immature, and then eventually when they go into these large industrial scales there has to be a level of maturity. Because it’s not like just adding more water to the soup. There’s clear scientific engineering and chemistry and physics that say, from making a 1-liter batch, for me to make 10, 100, 1,000, 10,000, 100,000, it’s not just adding more liquid to the vessel.
How similar is COVID-19 to other coronaviruses such as SARS or MERS, and how does that affect the research of COVID-19?
Usually within the coronavirus families, it’s very known that there are a lot of coronaviruses that circulate and infect humans ... in a way that doesn’t cause these outbreaks or pandemic-type events. We definitely know that these new ones, meaning the SARS and MERS and this COVID-19 virus ... originate from a different route. Therefore they start there being very pathogenic to humans. But knowing and advancing solutions that look at not only the less pathogenic—people also do studies on specifically understanding the bat coronaviruses or the camel coronaviruses—we learn from it. So that’s why research and development is very important and shouldn’t stop even if we don’t think that there could be another outbreak in the future. Which is not really ever the case. We need to always assume there are going to be others. Today we’re talking about coronavirus outbreaks, but there are many other families too. So any body of evidence we continue building ... will always accelerate how we respond to [viruses].
What are some risks associated with the accelerated vaccine development timelines we’re seeing at this time? What could have sped up the process?
You are pressuring those who have to evaluate to make decisions that in a normal way of business you wouldn’t because you have more time. Of course you have more risk. ... I trust 100% [in] our regulatory bodies. The people who conform the teams within the [U.S. Food and Drug Administration], for example, are teams that operate with their mission to ensure that their decisions are based on robust and strong scientific evidence. Not hearsay, not because they have to go fast. So I trust that process and that system. It’s challenging that they have to make this in an accelerated manner, but I think we as people have to trust at some level that they’re experts. But it would be great if they didn’t have to, or that they had to do it with a little more body of evidence under their belt. ... That risk however, is we are human beings. We make mistakes, and hopefully we try to put a lot of barriers such that we mitigate the severity of the mistakes.
Will this crisis change the traditional approach to funding and manufacturing vaccines?
I certainly hope so. It would be a shame that after all this, with all the suffering that we’ve seen, that then we realize a year later that we all went back to the same old business of disregarding the importance of setting up a sustainable business plan to advance research and development. We’re in the same boat as everybody. For vaccines, for public health, for epidemiology, for therapeutics. Granted, vaccines are very long-term and certainly are ideally the best-case intervention because it’s a preventative intervention. But ... there has to be parallel activities for not only ensuring therapeutics, diagnostics, public health, epidemiology, surveillance, education, training of our health providers, improving the health systems. Even how do you manage stockpiling of [personal protective equipment]? I think we’re going to have many lessons learned that we’re going to have to figure out here.
What do you think of the Houston area’s response to the crisis?
It’s amazing, right? Of course nothing is ever perfect, but the response of our medical center, it’s been stellar. ... There’s challenges with the diagnostics, with our city and county health departments, but we have some very bright and very passionate and dedicated teams. It’s hard because everything is so decentralized, but at the same time you don’t want to necessarily centralize everything because of preventing the wrong decisions. So you have to balance that ability. I’m a big proponent of creating alliances, both in the public-private sector, in the for-profit and nonprofit sector, and I think that’s the best that we can do.
What else would you most want people to know about vaccines?
Vaccines work. We’ve known this for hundreds of years. It’s the best solution to prevent very damaging infectious diseases. I hope people around the world reinvigorate their trust that vaccines are the best public health intervention. Unfortunately, [it’s] sad that we have to reaffirm this trust through a situation like this outbreak and pandemic. And we have to support the process and support that research and development and science is as important as many other things.
