IRA FLATOW: This is Science Friday. I’m Ira Flatow. At the beginning of 2020, there were no vaccines available, much less approved for COVID-19. But now in the first weeks of 2021, we have two, as well as a pipeline of dozens of vaccine candidates in clinical trials. As doses become available for frontline health care workers and the broader public, trust is a concern. We’ve even heard from listeners who wonder if the sped-up timeline or the novelty of mRNA are compromising safety.

TOM: I think I sort of understand how our current vaccines for smallpox work. But I’m not sure I understand what it is that happens with these mRNA vaccines.

ARNOLD: How much confidence do we have in the efficacy of this treatment? Primarily due to the fact that it was pushed so fast.

ISABEL: I’m a pediatrician in West Bloomfield, Michigan. Even among the community of parents who accept all other vaccines, there is some hesitancy. There should be a way to explain how the streamlined vaccine approval did not sacrifice safety considerations.

IRA FLATOW: Thanks to listeners Tom, Arnold, and Isabel for their comments on our Science Friday VoxPop app. And while SARS-CoV-2 feels like it came out of nowhere, these vaccines did not. They rest atop years of research, vaccine technologies with proven safety records, tweaked just a bit for this new virus. Even mRNA is not new. And we can thank the first SARS epidemic for much of that. Influenza and HIV vaccine research have also contributed.

Here to talk about it, two vaccine researchers with their own COVID-19 vaccines in the pipeline. Dr. Maria Elena Batarseh is Associate Dean at the National School of Tropical Medicine, Baylor College of Medicine, and Co-Director of Texas Children’s Hospital Center for Vaccine Development in Houston. She’s done work on SARS, and is part of a project to make vaccines for COVID-19. Welcome, Dr. Batarseh.

MARIA BOTTAZZI: Hi, good morning, Ira! Very nice to be with you.

IRA FLATOW: And Dr. Rama Amara, Professor of Microbiology and Immunology at Emory University’s National Primate Research Center. He joins us from Atlanta. He’s been applying his expertise from work on HIV vaccines, also in the name of a COVID vaccine this year. Welcome, Dr. Amara.

RAMA AMARA: Hi, Ira. Very nice to be with you.

IRA FLATOW: Nice to have both of you with us. Let me do a time warp. Let’s do a time warp back to, let’s say it’s January 2020, Dr. Bottazzi, and you’re researching SARS and MERS, let’s say. And you’ve just heard about a new virus with pandemic potential. Tell me what the vaccine researchers do first.

MARIA BOTTAZZI: Absolutely. So in fact, it was more like December of 2019, when we already were hearing about this pneumonia-like virus. So the moment, January 11, we got the sequence that it was a SARS-like coronavirus, we took that sequence and compared it in that case for us to the SARS sequence.

We saw that both sequences were around 80% similar. And we tinkered it very quickly because we already knew how to work with it from our SARS experience. And honestly, I have to tell you, what we used to do for SARS that took us three, four years, we actually managed to do it in three, four months, because we knew exactly how to manipulate the new sequence.

So that’s what we did first. We looked at the sequence, took it, synthesized it, and put it into our yeast expression system to be able to make a recombinant protein.

IRA FLATOW: So your lab was already ready to get working on this.

MARIA BOTTAZZI: Absolutely. This is what we were trained for. Our center now has 20 years of operation. We have, of course, many other vaccines we’re working on. But we’ve already had 10 years of experience working on coronavirus vaccines, MERS as well as SARS, as you mentioned.

IRA FLATOW: And Dr. Amara, you were working on HIV vaccines before pivoting to COVID candidate. What could you apply from this work on the HIV vaccine to this virus?

RAMA AMARA: Absolutely. So there is a wealth of information that we learned from the HIV vaccine development. We are interested in using both a neutralizing antibody as well as cytotoxic killer T cells, as well as helper CD4 T cells against the virus. That would give you a broad coverage from the immune system to attack the virus from multiple fronts.

And we learned a lot about the safety of this, and how to deliver it, and how to make high levels of this SARS virus protein when a vaccine is delivered. And we also know that what kind of immune responses the vaccine induces when it is given. Considering all that, when we decided to make a coronavirus vaccine, we could jump right into it, and then made a vaccine within a few weeks.

IRA FLATOW: So in other words, you already knew how to tweak the immune system to respond to the HIV vaccine. And you adjusted that for the new vaccine.

RAMA AMARA: That’s correct.

IRA FLATOW: So the success of the COVID-19 vaccines stem in large part from the work that’s being done on the HIV vaccine.

RAMA AMARA: I absolutely believe that. Because a lot of the money that invested in the HIV vaccine development and paid off in making the COVID-19 vaccine, for example, whatever AstraZeneca is using. Even [INAUDIBLE] and Pfizer and BioNTech and J&J, all these platforms that have been used are actually developed for HIV.

So all of these platforms were in [INAUDIBLE] too, right? So all these were developed for HIV. And then because so much knowledge existed, now we are all able to quickly apply this for COVID-19.

MARIA BOTTAZZI: And I don’t know if you realize, but the clinical trial networks around the world where these vaccines actually are being evaluated, actually are HIV vaccine trial networks. Yeah, so they really mobilized all the HIV’s infrastructure, not only technology, but the infrastructure. And that has given even a lot of the low middle income countries the opportunity to evaluate some vaccines, because they just plugged into an infrastructure that was created with HIV funding.

IRA FLATOW: Do you think that success with the COVID-19 vaccine is going to spur development of an HIV vaccine?

RAMA AMARA: In general, HIV vaccine program has been so slow because they follow standard vaccine development path. I’m hoping that now the experience with the COVID vaccines, I think they would actually try to change things to speed things up.

IRA FLATOW: It seems that neither of you have been working on mRNA vaccines. But it feels like these are the stars of the vaccine hunt, and kind of seem to come out of nowhere as a technology. Where were mRNA vaccines being developed before COVID-19, Dr. Bottazzi?

MARIA BOTTAZZI: I have to say that in fact, our laboratories do work on the RNA technology. We opted for not applying it for COVID-19, mostly because our center also is very interested, as you see, because we collaborate with global health entities to make a vaccine also quite accessible, affordable, safe, of course, for low middle income countries.

And we know that there’s still a little bit to go to make these vaccines using these new technologies, not only large scalable, but also maybe even affordable. And they’re a little bit more difficult, as you have been hearing about, even cold chain manipulations. But ultimately, the role of the RNA vaccine is similar to eventually what the protein-based vaccine does.

What you’re giving your body is a code that can become a protein in your body. And then the protein, really, is what induces your response against it, and therefore protect you. So I think that ultimately, the end goal is the same. The use of these RNA technologies– which, by the way, they have been being evaluated for years now. It’s not like they’re brand new either.

They may not have ever been licensed before, but they’ve been evaluated for even Zika virus vaccines, and even rabies vaccines. There have been trials already using those technologies. Eventually, they may take on around the world, as more people use them and learn how to make them. They may become even more cheap to produce and more scalable.

So I think overall, whether it’s an RNA vaccine, whether it’s a viral vector like Dr. Amara’s using, or a protein-based vaccine, or even live attenuated or inactivated vaccines. What we were very lucky is that this is a coronavirus, and we already knew exactly what to tackle. We knew that the vaccines had to be produced targeting the spike, or a piece of the spike. And I think that also is the reason why we were very quick at producing these vaccines, because we didn’t have to search for what candidate to tackle.

IRA FLATOW: The COVID-19 vaccines that are going into arms now took less than a year from start to finish. I understand it’s rare for a vaccine to be approved within five years. How much did money allow us to save time?

RAMA AMARA: I think it was a very critical piece in this big picture. Typically what happens is that we make a vaccine in the laboratory, we test it in the animals, show it is inducing the desired immune response, and it can provide protection against a [INAUDIBLE] challenge in the animals. And then you go into the human trials through initial phase I study, where you look at the safety, and the phase II. There you look at whether you are able to get desired immune responses in a few hundred people.

And then going to the phase IIB, phase III study, there we will test for the effectiveness of the vaccine in thousands of people. And once that is done, there will be plans to also scale up the manufacture of this vaccine, of any vaccine. So this takes a lot of time. Each step takes at least a year. There are multiple steps that are involved.

So because organizations like the [INAUDIBLE] invested in manufacture and manufacturing these vaccines, even before we had any data that these vaccines would generate the desired immune response and provide protection. So it was a big gamble we had to take. [INAUDIBLE] talking about the field in general.

So that really paid off. If they have to do it in a traditional way, this would not have been possible in a short time.

IRA FLATOW: And we keep hearing about hesitancy of people to take the vaccines on, safety concerns. You heard some of our listeners mention this at the top of our program here. Even after all the trials and the other research, even after panels of experts have given intense scrutiny to the vaccines that have already been authorized. Maria, is one year of safety data really as good as five or more years?

MARIA BOTTAZZI: Well, I think that you have to remember that when you initially launch a vaccine and you rely on not only the phase I, phase II, and even phase III safety data. I think we’re talking that it’s already thousands of people that have received such vaccines.

And so safety, usually if there’s going to be something quite [INAUDIBLE] is going to really show up pretty quickly. What we need to remind everyone is that safety evaluations don’t stop ever, even after indeed they get even licensed. Right now we’re under emergency authorization, which of course, they’re still considered experimental. But once the companies reach the entire full licensure, we still do a lot of what we call post-marketing surveillance. So surveillance never, never ends.

What I also would like to remind everyone in the context that we’ve been discussing that it’s not the first time that we’ve been evaluating coronavirus vaccines in the clinic. And we’ve been doing this with also the SARS vaccines that have reached the clinic, or even the MERS vaccines that have reached the clinic. And even though we were never given the opportunity of fully advancing the vaccine development for those two, mostly because the virus was pretty much controlled, and making these phase three clinical trials, you require a level of virus circulating in the community, right to see the efficacy.

So we already also had a lot of safety evidence from prior trials from all of our research on coronaviruses before. I think we should remember that now, also not only RNA vaccines, but many of these other platforms of vaccines, there’s now millions of people that have been vaccinated. So I think that it gives you quite a strong assurance that they are safe, I think.

And most likely, they all will work, some better than others. Some will work better for some demographics, maybe even some regions of the world. But I think right now, they’re really going to be the game-changer, to really try to reduce the virus circulating in our communities, while at the same time really offloading some of the health care pressures that we’re having, because people are going to have a lot less symptoms using these vaccines.

IRA FLATOW: I’m Ira Flatow. This is Science Friday from WNYC Studios. We’ve talked about the existing research. We’ve talked about the money. But are there other ways, the effort to create COVID-19 vaccines were able to happen faster without compromising quality, Maria?

MARIA BOTTAZZI: So, three things right? The technology that allowed us to know that the sequence of the virus was done in less than a week, it’s amazing. So technology in general is accelerating. So not only technology and the sequencing, but also technology and being able to track the virus. And we could have done a little bit better with the diagnostics.

But at least we know technology is key. That is very different what we have today from even 10 years ago. The fact that there’s so much virus circulating, unfortunately, in our communities allowed these large phase III clinical trials to really reach what we call clinical endpoints quicker, because people were getting infected. So therefore, they could measure how well the vaccines would reduce the clinical symptoms.

And clearly what Dr. Amara said, that the influx of money to advance manufacturing, because usually companies wait until they know the vaccine works before they even say, OK, now I’ll invest in making bulk loads of the vaccine. The fact that they made a lot of vaccine production ahead of even knowing whether they would work, that probably skimmed off another couple of years. So those are really the three main aspects that I think have really had a drastic reduction of the timeline.

IRA FLATOW: We have run out of time, so much to talk about, so little time to talk with you. I want to thank both of you for taking time. Dr. Maria Elena Bottazzi is Associate Dean at the National School of Tropical Medicine. Baylor College of Medicine Co-Director of Texas Children’s Hospital Center for Vaccine Development in Houston. Thank you for being with us today.

MARIA BOTTAZZI: Thank you so much, Ira. It was a great pleasure to share this with you and with Dr. Amara.

IRA FLATOW: You’re welcome. And Dr. Rama Amara, Professor of Microbiology and Immunology at Emory University’s National Primate Center in Atlanta. Dr. Amara, thank you for taking time to be with us today.

RAMA AMARA: Thank you, it’s my pleasure, and it’s also a pleasure to be with Dr. Maria.

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