Watch the replay of this event held on April 20, 2022

The rapid development of safe and effective Covid-19 vaccines has led to the vaccination of more than half the world’s population over the past two years — an unprecedented public health achievement. But the uneven distribution of vaccines has created a stark gap in protection between different countries: While more than 70 percent of the citizens of Brazil, Canada and China are fully vaccinated, for example, fewer than 1 in 10 people have received a single dose in many African countries. In addition to creating a humanitarian crisis, this unequal distribution of vaccines favors the rise of new viral variants, threatening public health everywhere. Why has COVAX, the international initiative created to make sure all countries have access to vaccines, failed to reach that goal? What can be done to get doses to vulnerable populations?

Watch this conversation with Maria Elena Bottazzi, co-director of Texas Children’s Hospital Center for Vaccine Development at Baylor College of Medicine, and Jerome Kim, director general of the International Vaccine Institute, to learn how we can achieve more equitable vaccine distribution — and why that’s necessary to end the pandemic.

Speakers

Maria Elena Bottazzi

Maria Elena Bottazzi, PhD, Baylor College of Medicine

Maria Elena Bottazzi is an internationally recognized tropical and emerging disease vaccinologist and global health advocate. She is the co-creator of a patent-free, open-science Covid-19 vaccine technology that led to the development of Corbevax, a Covid-19 vaccine for the world. Bottazi leads partnerships that advance vaccines for diseases that disproportionately affect the world’s poorest populations, catalyze policies and disseminate scientific information to diverse audiences. She also serves as co-chair of the Vaccines and Therapeutics Taskforce of the Lancet Commission on Covid-19. Earlier this year, alongside vaccine researcher Peter Hotez, she was nominated by US Rep. Lizzie Fletcher, D-Houston, for the Nobel Peace Prize.

Jerome Kim

Jerome Kim, MD, Director-General of the International Vaccine Institute

Jerome Kim is an expert on the evaluation and development of vaccines and director general of the International Vaccine Institute, a nonprofit devoted to research on vaccines for poor countries. Previously, Kim held the post of principal deputy and chief of the Laboratory of Molecular Virology and Pathogenesis at the US Military HIV Research Program. He also served as the project manager for the HIV Vaccines and Advanced Concepts Evaluation Project Management Offices for the US Army in Fort Detrick, Maryland, and led the Army’s Phase III HIV vaccine trial, the first demonstration that an HIV vaccine could protect against infection.

Moderator

Emily Underwood

 Emily Underwood, Science Content Producer, Virtual Events, Knowable Magazine

Emily Underwood has been covering science for over a decade, including as a staff neuroscience reporter for Science. She has a bachelor’s degree in science and technology studies from Brown University and a master’s degree in science writing from Johns Hopkins University. In 2016-17, Underwood was a Rosalynn Carter Fellow for Mental Health Journalism, and her reporting has won national awards, including a 2018 National Academies Keck Futures Initiative Communication Award for magazine writing.

About

This event is part of an ongoing series of live events and science journalism from Knowable Magazine and Annual Reviews, a nonprofit publisher dedicated to synthesizing and integrating knowledge for the progress of science and the benefit of society. Major funding for Knowable comes from the Gordon and Betty Moore Foundation and the Alfred P. Sloan Foundation.

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Video Transcript:

Emily Underwood: “Hello. Welcome to ‘A path to Covid-19 vaccine equity,’ our event today. Today, we’re going to talk about why more than 2 billion people still haven’t got a single Covid-19 shot and what can be done to increase vaccines around the world, especially in low- and middle-income countries. This discussion is brought to you by Annual Reviews and Knowable. I’m Emily Underwood, science content producer for Knowable. I checked my vaccine card this morning and I realized it’s been almost exactly a year since I got my first dose of the Pfizer shot, April 23rd, followed by a second shot and then a booster in November.

“We all know the grief and the loss and the uncertainty that this pandemic has inflicted — we all can share in that. But globally, we haven’t shared the burden of the pandemic equally or the protection that effective safe vaccines can offer. While more than 11 billion doses have been administered worldwide, so far only about 15 percent of people in low-income countries have received a single shot. Meanwhile, the majority of people in wealthy countries are fully vaccinated and, like me, nearly half have gotten at least one booster.

“So, today, I am honored to welcome two leaders in vaccine development who find that disparity unacceptable. They have spent their careers trying to fix the systems that created the disparity and they have a vision for transforming vaccine development and manufacturing, and how to make it more equitable. So please join me in welcoming Dr. Maria Elena Bottazzi, associate dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston. Hello. And then also Dr. Jerome Kim, director general of International Vaccine Institute based in Seoul.

“It would take me half this event to list all of their accolades, so I just want to note a few highlights. Within a few months of the pandemic start, Dr. Bottazzi had released a protein-based vaccine that she codeveloped with her colleague, Dr. Peter Hotez. They gave it to the world patent-free, and we will talk more about why that vaccine only recently started being produced and why they chose to use an older technology to make it.

“First I want to welcome Dr. Kim, director general of International Vaccine Institute, an organization based in Seoul, South Korea, which includes more than 37 signatory countries. Dr. Kim has been instrumental in the development of HIV vaccines and is a dedicated vocal leader in the rollout of vaccines for Covid-19. I’m so looking forward to hearing their perspectives today, and I’m sure you are too. And I’m seeing people from all over joining us — this is really exciting.

“A few housekeeping items. We will be recording this and sharing it for free. You can replay it after it’s over and share it with others. We’ll include a list of resources along with the recording. So please do feel free to share relevant links in the chat. As we’ve been saying in the chat, if you find you can’t hear the audio, please refresh your browser. You can put your questions in the question box at the bottom of the screen. After 40 minutes, our editors will select from the questions that you post.

“Now, after the chat, we hope you’ll continue the conversation on social media, perhaps by sharing something that you learned from today’s conversation. Did this event change your mind about something? Did it make you think about the issue in a new light? Please tell us about it. You can tell me on Twitter @em_underwood and the Knowable-Annual Reviews team about it @KnowableMag and @AnnualReviews. If you want to help us keep making these events and high-quality science coverage freely available to all, please consider donating at knowablemagazine.org/donate. The best way to find out about our future events and everything else that Knowable publishes is by signing up for our newsletter, and there’s a link to that in the chat.

“OK, let’s get started. In the early days of the pandemic, there were lots of proposals for how to distribute Covid-19 vaccines ethically and equitably. The World Health Organization suggested that countries should receive vaccines proportionally to their populations. Bioethicists proposed that distributing vaccines according to the scale of the harm that could be avoided by vaccination, both in terms of preventable deaths and the social and economic harm that lockdowns would inflict by closing schools, for example. So by the logic of that second argument, poorer countries and populations should have gotten vaccines first, but that’s not what happened. And I would like to hear from Dr. Bottazzi to begin with, from your perspective, what happened instead?”

Maria Elena Bottazzi: “Well, first of all, thanks so much, Emily, for inviting me and Jerome to have this conversation with you, which by the way, Jerome Kim is one of my favorite people around the world. I’ve learned so much from you, Jerome, for not only during this pandemic, but even before. So it’s just a pleasure to be next to you talking about this. Well, what is my perspective? My perspective is that we all found ourselves in such an emergency, an urgent situation, seeing how this virus was really creating havoc at all levels, right? Not only of course, with deaths and health, but also economically. And we were bombarded with this notion of having to close down and stay at home and that we couldn’t even see our family.

“It was pretty stressful, if you can imagine. And so the reaction, and I think it’s the normal human reaction, is what can we put out there the fastest, the quickest possible way that we can get a solution out there. But maybe not necessarily thinking of how could we eventually make this rapid response to the point where it could be affordable, acceptable, scalable. Certainly we were trying to develop it in the midst of the crisis, so I think at the end, the decisions were skewed for speed, of course, because you needed to have solutions fast that we needed to make enough to, like you said, try to reach at least the most at-risk populations.

“But we very rapidly realized that the virus went just ahead of us too quickly, and it just got out of hand. And therefore the technologies that were in development early on, eventually we realized that they would not be sufficient, that they would be in some areas costly. And that’s how we started seeing how those who had the economic powers in the world started pre-acquiring, securing their inventories. And eventually the people in the low-, middle-income country settings were left behind, because clearly it was not equitably divided on the basis of availability at that time and also the cost at that time.

“So I think it was just that the pandemic evolved to a point where it was really out of hand. The detection wasn’t enough to block it. And the products that we were trying to advance were just not going to be enough. And eventually, they ended up being also too costly. So maybe Jerome can also comment on his perspective.”

Jerome Kim: “Thank you for the kind invitation to appear on this. I didn’t know about Knowable Magazine, and now I do. And I think I’m going to log on and try and find out a lot more about it. And thanks again to Professor Bottazzi for that introduction. Actually, very soon after the pandemic started, we got a call from Baylor, Professors Hotez and Bottazzi, to talk about a vaccine that they had already developed for the original SARS-CoV-1 and how we thought that that might be useful. And we put together a grant proposal and it didn’t get funded, unfortunately.

“And it goes to some of the points. Here was something that was in hand, that probably would’ve cross-protected, that we wanted to test and we just couldn’t get funding. And I’m glad that the Baylor Group continued in their search for funding. And it came up with funding from some really unusual sources. And not the typical ones, not the CEPI, not the US government, but I think it was Tito’s Vodka gave them a huge grant that really allowed them to take that vaccine forward.

“When you look around the world, who’s making 75 percent of the vaccines used for pediatric immunization around the world? It’s not the big pharma companies, it’s Indian vaccine manufacturers. Did they get any of the initial funding from CEPI or other organizations? No. Would it have been beneficial had they been worked with and gotten that kind of funding? We don’t know. It’s one of those things where, as we look at future responses, we’re going to have to go to companies that routinely manufacture hundreds of millions and billions of doses of vaccine, because that’s the kind of volume that we need to respond to pandemic.

“IVI has worked throughout its history with technology transfer. So we’re comfortable and familiar with the organizations around the world that have local regulatory approvals from say, DCGI in India or the Korean Ministry of Food and Drug Safety. And that can be referred to WHO for what we call pre-qualification or in the emergency situation, UL or emergency-use listing. And we know that those organizations provide huge quantities of vaccine and are capable of it, but what do they need? They need funding to do the research and development necessary, and they tend not to develop things at risk.

“We know what they can do, but would it have been better to engage them sooner and have gotten some of these products out faster and in much larger volumes? And again, this just gets to one of the lessons learned, is that there are lots of vaccine manufacturers and around the world, the people who manufacture the most vaccine are not the high-tech pharma companies, but instead the developing-country vaccine manufacturers.

“So our experience: IVI decided not to do its own vaccine. What we decided was to help any organization that needed help in any of the areas that IVI could work in, which go from testing vaccines in animals, doing challenge studies in animals, doing phase one to phase three clinical trials, doing phase four effectiveness trials, helping companies or organizations with WHO approval pathways or the submission and preparation of dossier. And so two dozen companies now have been partners in development of vaccines and we’re testing vaccines for companies that have committed 1 billion doses to COVAX, the global mechanism for distribution of vaccines. And I think that was our choice, and I think in the end it was the right one.”

Emily Underwood: “So it’s interesting that you …”

Maria Elena Bottazzi: “Emily …”

Emily Underwood: “Hey, go ahead please.”

Maria Elena Bottazzi: “I was going to, well, first thank Jerome for the plug, right? And I think I should clarify to the audience again, the fact that indeed you are right, Jerome. We had a vaccine already — 10 years of working on SARS and Merck vaccine prototypes. We indeed had something that, I agree, we could have potentially even deployed almost immediately to evaluate its potential of even cross-protecting against this SARS-CoV-2 virus. And I think that looking now back, three years ago, why was it that indeed we couldn’t get the interest from the big funding mechanisms like governmental and certainly CEPI? And it’s because again, there was this mentality that the technology of bringing a recombinant protein technology to the table was not a speedy technology, that it would still take months to develop, right?

“Because making proteins, you cannot make them in a week like you can make a sequence of a RNA virus, right, of an RNA piece. And so there was this notion that they needed to find something that was a lot faster. And then you’re right. I think then the other reason why is because they didn’t realize that they were not including all these network of developing-country manufacturers that three years ago, they certainly did not know how to make RNA technology. And some of them even potentially, adenovirus technology, but they clearly would know how to make inactivated virus vaccines or they would be able to make protein-based vaccines, but they totally got excluded to the discussion, right. And they were really fixated that they needed something that was quick, something that you can make and potentially, bring to the clinic fast so that they could eventually evaluate this very quickly.

“And they left behind that ecosystem of producers that had already other capabilities that they could have come, even if it’s a little later, but they could have brought in other alternatives. And now we’re seeing this, right? That finally, I think two, three years later, we’re now seeing that at least they’re paying some attention to the developing-country manufacturers and alternative platforms, which ideally could have been brought in earlier and possibly even contributed to this inequity gap if we could have just given the opportunity of codeveloping them at the side of these newer technologies. We don’t say that they should have been either or, I think the lesson is that they should have been all considered equal, not that protein-based vaccines are less important than an RNA or an adenovirus technology. Back to you.”

Emily Underwood: “I’d like to just back up a little bit and talk about the bigger landscape of vaccine production. You’ve mentioned Gavi, you’ve mentioned some of these other international collaborations around vaccines. But what was the landscape for the vaccine development before the pandemic hit and how has that changed and how is that affecting vaccine equity or inequity?”

Jerome Kim: “So I can …”

Maria Elena Bottazzi: “Well, I can start if you want by just, oh, go ahead. Go ahead, Jerome.

Jerome Kim: “No, no, please go ahead, Maria.”

Maria Elena Bottazzi: “No, go ahead.”

Jerome Kim: “Yes, so …”

Maria Elena Bottazzi: “I was just going to give it the perspective …”

Emily Underwood: “All right. I’m going to ask Jerome; I should have made that easier for you. Sorry, go ahead, Jerome.”

Jerome Kim: “Yeah, sorry. Sorry, Maria Elena. Globally, we have very innovative companies developing vaccines for high-income countries. And I think the other thing we recognize is that almost every problem that exists in high-income countries also exists in low-income countries; they may not realize it. Sometimes you have to prove that a country has Haemophilus influenza meningitis or severe invasive infections from pneumococcal, from Streptococcus pneumoniae. But once you look, you find it.

“And so all these vaccines that are developed by Pfizer, by Merck, by GSK, there’s a tremendous need for those vaccines in low-income settings where health resources are not sufficient. We can take care of Rotavirus diarrhea with hydration in the United States or Europe, but in a country that doesn’t have ready access to intravenous fluids, children die from dehydration. And the standard of practices that... you know, Rotavirus vaccine was approved by the US FDA in 2006. It was approved by WHO in 2009. It was recommended by SAGE in 2009. In 2022, 16 years after it was approved in the United States, 60 percent of the world’s children did not receive Rotavirus vaccine.

“The low-income countries are rather taken care of by Gavi, which has been just a remarkable driving force for getting vaccine to countries that really need it. But it’s middle-income countries that can’t afford to pay $20 a dose for a vaccine. So luckily now, so I guess 14 years into this, Bharat and Serum Institute, two large Indian vaccine manufacturers have now gotten WHO-approved Rotavirus virus vaccine, and the cost: $1.10 a dose. So this is a vaccine that can now be used, but those developing-country vaccine manufacturers selling hundreds of millions of doses at a dollar a dose don’t have the kind of model that will support intensive research-driven vaccine development.

“And so when it comes to something like a novel pathogen, they don’t have the funding available to do what Pfizer did, which is basically fund all of the development, or almost all of the development, on its own. But they do have manufacturing capability and they do have skills that will allow them to do product development, particularly for products that they’re very familiar with, maybe not RNA, but viral vector vaccines, protein-based vaccines and inactivated vaccines.

“And this is just another story: IVI was working with Sinopharm, which is the producer of 70 percent of the vaccines used in China. And they had in it, heat-inactivated Covid vaccine. It’s difficult, but we worked with them. We got together a proposal for support for phase three trial outside of China. And it was turned down, why? Because they couldn’t guarantee more than 300 million doses, which in retrospect, would’ve been 300 million doses that would’ve been very valuable in December, January, February, March, April of 2021.

“And now, of course, they’re making huge numbers of doses. They can make 2 billion doses a year of that heat-inactivated vaccine, but they were turned down for funding. And that made it more difficult to engage them in the things that are necessary, like WHO rules and requirements and making sure that the data were accessible and available in the way that we would normally do. So again, it’s not to say that Sinopharm’s vaccine should have been funded back then, but it’s lost opportunity. And it’s that lost opportunity in a pandemic that, unfortunately, results in delays and deaths.”

Maria Elena Bottazzi: “… Can I expand on that? Thanks, Jerome for that comment, too. And I have to say that is the reason why academic research groups like ours, I think that’s the key of the type of paradigm change that we want to do. So our example of having worked again with coronaviruses for 10 years, trying to create this so-called vaccine prototypes, but with the philosophy that we wanted to ensure that we would work on platforms that would therefore be suitable for transferring to these low-, middle-income country type of manufacturing companies. It’s key, because so we serve for them a little bit as the surrogate R&D that Jerome says that potentially they don’t have the funding or the time to be able to invest themselves.

“So our work that we did in partnership with, for example, Biological E was to indeed transfer a technology that enabled a company such as Biological E to be first-rate innovators and receive this R&D technology rough and crude, because arguably in our laboratories, we can produce a process that is at the 10-liter scales, for example. But they are going to eventually have to mature it, scale it, ensure that you can have reproducibility and eventually becomes an industrial scale to the point where today biological, it can make billions of the vaccine doses that we transfer to them.

“And so that’s what made the distinction, right? The distinction of not being a follow-on vaccine manufacturer that basically just receives already a mature technology from one of these multinationals that already are pretty much mature processes, but rather jumped over the R&D, because we did that, but enable a Biological E to be first-rate innovator and now call this vaccine as their own indigenous vaccine. And I think that’s really the premise of our vaccine center. We’ve been working on neglected tropical disease vaccines for more than 20 years, indeed with that mentality, right? That if somebody’s going to get incentivized at adapting, adopting and, eventually, developing these types of interventions and testing them and evaluate them, we have to remove as many barriers as possible.

“And so we need to give them something that it’s already within their capacity. So technologies that they already know, with people already trained for them, that they understand that they can certainly adapt very quickly, that there’s no barriers of intellectual property. And at the same time, give them that opportunity of making them indigenous and that they eventually can call them as their own. And that it’s not like it came from somebody else. Back to you.”

Emily Underwood: “Technology transfer is obviously a huge gap here, and an important thing to focus on. I’m wondering though, there’s also been a lot of focus on the need for wealthy countries to live up to their promises to donate and share doses in a timely fashion. And I’m wondering if you can speak to how much is that versus the technology transfer is the issue, or is it everything at once? And what are some of the repercussions of the failure to deliver the promised doses on time?”

Maria Elena Bottazzi: “Well, I think in that perspective, you have to remember that normally when a manufacturer engages into a development path, they don’t invest into the large-scale manufacturing until they really know that the product actually performs, right? So I think the major distinction of this during this pandemic and what made it actually, which was very important is that all the different vaccine manufacturers around the world decided that they would advance that manufacturing scalability and the industrial scales, right? So that they would have them ready even before they would even know that the vaccine product would work. And that’s a big deal, right?

“That’s a big risk for the vaccine manufacturers to say, ‘I’m going to make these millions and millions of doses. I don’t even know if it’s going to work, but I am going to risk it.’ Now, yes, many of them had the subsidies of doing it. Others, maybe less subsidized of doing it. But ultimately, that was really decisive, of making sure that we had at least the amount of vaccines that we were able to deploy early on. And that was all at risk, right? Now, again, we didn’t have enough because some countries of course had more economic power of acquiring them and securing that inventory that was already being produced. And that’s why, however, eventually still the middle- and low-income countries were left behind.”

Emily Underwood: “Thank you. Maybe this is a question for Jerome, just as a follow-up. Where do you think the focus should be right now in terms of international aid and investment in building up capacity for vaccine development and distribution?”

Jerome Kim: “Yeah. And so can I just go back to a little bit of what Maria Elena was saying?”

Emily Underwood: “Absolutely. Please.”

Jerome Kim: “Yeah. The high-income countries, and it’s actually probably the US in particular with Operation Warp Speed really took a novel approach, which was to say, ‘We’re going to de-risk it for you. Here’s several — what? — $20 billion worth of funding and at the end, if you’re successful,’ and they funded a lot of companies because they figured, ‘Well, 1 out of 7 might be successful, 1 out of 9 might be successful.’ But it turns out that almost all of them were successful. So they had a lot of vaccine and they paid for it upfront. And that allows the manufacturer to do a lot of things faster and with less risk to the company than they would normally take in a five- to 10-year development cycle.

“CEPI did the same thing, but with $1.5 billion. Other countries around the world stood there, and really Operation Warp Speed was for the United States. It did develop vaccines that we can use all over the world, but the initial aim of that program, which is rightfully so, I guess, because it was US money, was around the United States. Would we have been able to plan for something? I know I call it a tithe because it’s 10 percent, but many religions around the world have the same concept of giving a percentage for less fortunate people. And so could we have reserved 10 percent of production initially to cover the greatest risk groups in low- and middle-income countries? And could we have done it without much additional loss to the high-income countries that were deploying these vaccines as quickly as they could?

“And we created COVAX instead, which I know we’ll talk about, which is an amazing mechanism. It’s the first time innovative technology has ever really reached low- and middle-income countries in the first year of introduction. There are lots of issues at play here, and really the remarkable rapidity of development was a tribute to the wave we’ve approached funding for companies. There are lots of consequences from not being equitable in distributing vaccine.”

Emily Underwood: “Can you speak a little bit about COVAX? Maybe explain to our audience who may not know what that is. What is COVAX and what were some of its strengths and some of its limitations? Let’s start with you and then Maria.”

Jerome Kim: “OK. Yeah. So COVAX is a great idea. Remember how I pointed out that with Rotavirus vaccine — and actually it’s true with pneumococcal conjugate vaccine, with human papillomavirus vaccine — it takes decades to get out to low- and middle-income countries and they knew that this was going to be a problem for Covid vaccines also. And they also believed that there was going to be a problem in low-, middle-income countries with infections and deaths, which we all knew was going to happen.

“So the World Health Organization, CEPI (the Coalition for Epidemic Preparedness Innovations) and Gavi, the vaccine alliance, got together and the three of them — and so there’s no leader, there’s no person in charge, but the three of them got together and they said, ‘Look, let’s pool purchasing. Countries can contribute to the COVAX mechanism, and we will fund vaccine purchases for roughly 15 percent of a country’s need.’ Fifteen percent would actually supply vaccine for the elderly and for health-care workers actually in most countries.

“A hundred and ninety-two countries signed up, 90 countries were going to get the vaccine free of charge, which would’ve been a remarkable mechanism. They wanted to have 2 billion doses dispensed by the end of 2021; they were actually at about 800 million at the end of 2021. So it didn’t quite make its target. Countries, particularly high- and upper-middle-income countries were going off and making deals on their own. And that undermined the mechanism, and vaccine finally started to get to low-, middle-income countries. There were a couple of deliveries early on, but really the bulk of the vaccine didn’t get there till well after the summer.

“The mechanism didn’t work as smoothly as we wanted. The purchasing, the availability of funding was not sufficient for what COVAX needed in order to get to the part of the line, the queue for vaccine doses, that they really needed to be in. And so it was a great idea and we should improve it. Because if this is a mechanism to get HPV and Rotavirus into a conjugate or if we develop a vaccine against respiratory syncytial virus to get this out quickly, COVAX would be a wonderful mechanism to do that if we can make it work and work better.”

Emily Underwood: “Thanks. Maria Elena, can you talk a little bit about the repercussions that you see of how COVAX fell short and how you think that mechanism could be improved in the future?”

Maria Elena Bottazzi: “Yeah, absolutely. And I agree with Jerome. The idea was stellar, right? The challenge was that they had to fundraise at the same time they were trying to create the infrastructure. So I think the lesson learned is that the COVAX concept should already have clear resources that would then enable them to be able to accelerate, right? Because I think they were fundraising while they were trying also to identify which vaccines were going to be able to be supported through the COVAX. But then I think it’s the same, what I mentioned at the beginning is that they assume that if we were all going to be able to deploy multiple tools to block this virus, whether it was including, of course, all the non-pharmaceutical interventions while we were developing, of course, clinical management or understanding the clinical management. Of course, developing vaccines and then drugs, that it would have been enough by really covering that 15 percent of the world’s population that we would be able to, I guess save a lot of the high-risk people, but that then we would potentially be already done, right?

“And I think when we started seeing that this pandemic was again, getting out of hand and the fact that not only we were not getting those 15 percent coverages with the vaccines because again, of the push and pull of who was acquiring them, who was giving priority. And eventually, the delay. The fact that there was no more funding, which vaccines were getting authorized. And of course, accepted through the COVAX. Eventually, the countries got really stressed and frustrated because they started seeing that not only they needed to get vaccines faster, that they had to, like Jerome said, start to do negotiations on the side, but then they had realized that 15 percent of coverage for their population was not going to be enough. That at some point there were going to have to find vaccines that will also cover the rest of the 70 percent of their population or the 60 percent of their population.

“And then when we started seeing that, not only we would need two doses of a vaccine, but then it would be a booster dose. Now, a fourth dose then introducing also pediatric indications. So I think that it just ultimately got out of hand and COVAX was just not rapid enough. But I agree, and unfortunately it should have worked because it was a framework that you could ensure quality, that you would ensure equity, that you would ensure access. But at the end of the day, I think the world, it was not quick enough. And it’s also because the vaccines were not produced at scale, they were costly and eventually there was also no money. And that the countries were just frustrated and they started to look for alternatives.”

Emily Underwood: “In terms of the decision to favor certain technologies over others, what have we learned from this pandemic about picking winners early on?”

Maria Elena Bottazzi: “It’s a very good question. And again, we should never put all our eggs in a single basket, right? And I know that we were very lucky that it was a coronavirus. We even knew even before this Covid-19 started that a coronavirus vaccine was possibly an easy task to achieve. We had a lot of evidence from SARS and MERS, right? So thankfully, and we knew that we would be able to possibly get some vaccine rolled out pretty quickly, but we skewed it with, again, not diversifying the … technologies. We should have said, ‘Let’s support the RNA technology, support the viral vector technology, support the inactivated virus approach and support the protein-based approach,’ because ultimately we didn’t really know which ones were going to work.

“Now, we know that all of them work at some level more than others. But there was also a question of what the ecosystem of production is out there. And like with any new technology, you need time to ramp up, learn it, reproduce it, transfer it, versus older technologies you already have an ecosystem. So we could have maybe balanced out that newer technologies were going to be suitable for certain areas because of its scalability and cost, and coal chain challenges while others would have been reachable better in other regions of the world. And that’s how we saw indeed, like when Jerome mentioned that the Chinese vaccines, which primarily are on the basis of holding activated virus approaches, those really flooded the low-, middle-income countries, right? Because they were the affordable and they were the ones who were reachable to them. And now, unfortunately we see that may not perform as well as these variants have been arising, so now we need to bring additional solutions also to the world.”

Emily Underwood: “Thanks. Jerome, is there anything you want to add to that about how to invest intelligently in multiple types of vaccines at once going forward? How do you think that should be approached?”

Jerome Kim: “Yeah. So it was ironic, because today I just gave a talk on the effectiveness of all the different vaccines. And it’s actually remarkable when you look at effectiveness and not infection, but actual prevention of hospitalization and death. And even against Omicron, the vaccines have not done that badly. You do need to be fully vaccinated, which at this point means vaccine plus a booster. So when you think about what Covid has done, amazing innovation, right? These platforms, there have never been an RNA vaccine. There have been one minor example of an adenovirus-based vector. New adjuvants, like the adjuvant that Bharat put in its whole inactivated virus. Vaccine had never had widespread use before, the first approved DNA vaccine.

“Another Indian company called Zydus Cadila, tremendous innovation on the one hand. On the other hand, what are the vaccines? The most commonly used vaccines are the whole inactivated ones globally. Sinopharm, Sinovac, 4 billion doses, more than Pfizer and Moderna. AstraZeneca is definitely up there. So these are not the fancy technologies; these are the scalable technologies that are being used globally, not necessarily in the United States or Europe. And they are. The problem with China, the problem with Hong Kong, is not that their vaccines are failing, it’s that they didn’t vaccinate the elderly people. They did not vaccinate the population at greatest risk from dying if they acquire Covid-19.

“And this gets to the idea that tremendous innovation and proof of concept — remarkable — and so that’s good. We have RNA vaccines and viral vector vaccines now well established, but the tried-and-true technologies like protein technology. My next boost I hope will be a protein with one of the new adjuvants that will give you maybe higher and longer levels of protection. And the other thing I think to remember is we shouldn’t have thought that vaccine development was going to end when we had an approved vaccine, because the evolution of the virus and in part potentially driven by inequity, the lack of vaccination in Africa could have contributed to the arrival of these new variants. Omicron of course came from Africa, or was first uncovered out of Africa in a country, South Africa, which actually does to its credit do monitoring.

“But there were other countries, in the month before Omicron appeared, this is something Maria Elena’s group’s has written about: the diagnostics equity gap. They contributed less than 200 full-length sequences to the global database. While Europe contributed 70,000, North America contributed 50,000, Africa contributed 200. So we weren’t looking for recombinants. We weren’t diagnosing outbreaks and we know variants come from outbreaks. So we should have continued to develop vaccines, we should have continued to screen for the variants. I think we’re going to be much better about it in the future.”

Emily Underwood: “Thanks so much. So the time’s flown by. It’s actually almost time for audience questions where it’s time to open this up. But first I just wanted to thank everybody who has been tuning in and sharing their questions. Please do share your questions in the question box. If you’re enjoying this event and you want to join us, again, please sign up for our newsletter, follow us on Facebook and Twitter. A quick plug for our next event, which will be in late June — June 29th. We’ll be talking about the origins of the Grand Canyon, one of the coolest places on Earth.

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“OK, let’s turn to audience questions, and thanks again, Jerome and Maria Elena. This has been wonderful. OK, I think the first question I want to ask, from Pascal, is: ‘Is vaccine development over for SARS-CoV-2? How excited would Dr. Kim and Dr. Bottazzi be about a shelf-stable DNA vaccine to close the vaccine gap in low- and middle-income countries?’ Let’s see, Maria Elena, do you want to take that one first?”

Maria Elena Bottazzi: “Yeah, sure. So certainly it is not over. I think we still have, again, unfortunately, these variants that are circulating, so we are always keeping an eye and paying attention indeed to evaluate not only the vaccine that we have already developed as a prototype, but also looking at potentially the need of a strain change, if it’s necessary, or even combining different types of Covid-19 type of vaccines. But I think for us the work that we’re doing in our labs right now, it’s to try to see if we could design a vaccine that could even address potential future coronaviruses. So creating some broader, more universal coverage that could eventually even give us some protection of a coronavirus that maybe that we don’t even know.

“So I think that’s where we’re gearing ourselves up and there’s many different approaches of how we’re doing this. You would think that you could get the sequence, in this case, whether it’s the spike sequence or the RBD, the receptor binding domain, and then looking for a consensus sequence that could cross over the different lineages of the SARS-like viruses. Like we’re actually seeing some very interesting data in our preclinical models of just by combining SARS-CoV-1 with SARS-CoV-2 and how it amplifies and how it increases the durability and the coverage. So we’re looking at those designs and try to predict how can we make these vaccines better.”

Emily Underwood: “Jerome, do you want to add anything to that or should we move on to the next question?”

Jerome Kim: “Actually, so a slightly different take on this? I think it’s going to be important to remember that we are not only dealing with developing the new vaccine, but we’re going to have to understand the immune response to those vaccines in the context of previous vaccination and the context of infection or both. That prior exposure may shape future responses, so we’ll have to really think carefully. We are also collaborating with organizations that are developing what we call pan-Covid vaccines. So ones that will potentially protect against much broader strains and against pan, universal coronavirus vaccines, a much more difficult target.

“Imagine that these are all in the same group. So we definitely need to develop vaccines, but what kind of vaccines do we need to develop? We have to remember that we would ideally like vaccines that are broad, that you don’t have to change every six months or that don’t require boosts every six months. So not only significant magnitude of an immune response, but durable immune responses. We also might want to start thinking about what will actually decrease transmission. As the coronavirus has gotten more infectious, are there ways to approach mucosal vaccination that will allow a person or a vaccinated person to not spread the viruses as readily?

“And we really don’t understand what it would take to interrupt transmission. There have been some studies on household transmission, some interesting studies out of the UK, where they actually sent people home with diagnostic kits, but we really don’t understand that. So there’s a lot of improvement in these vaccines that we could do that will make it much more amenable to use in broader public health programs. And then finally, I think again, we really need to make sure that when we do it the next time that there’s equity in the distribution, because these new vaccines, when they come out, everyone’s going to need them.”

Emily Underwood: “Thanks so much. That’s really fascinating. We have a question from Cliona O’Farrelly — hi, Cliona — about economics. So what are the costs of death and infection versus taking the vaccine? What are the economic costs of this still-circulating virus? So, yeah. Would you like to take that first, Maria Elena, and or, yeah, or Jerome?”

Maria Elena Bottazzi: “Why don’t you start, Jerome?”

Jerome Kim: “OK. Yeah. So if you think about the cost in the United States, the average cost of hospitalization, according to the Kaiser Family Foundation, was $20,000. The cost of unvaccinated people during the Delta spike then was $14 billion. The cost of unvaccinated people in the Omicron spikes, these are vaccine preventable hospitalizations brought that total from $14-to-$30 billion. The problem in developing countries, and again, this would be where we’re focused because of equity questions is that if you look at the map of where there are cases of coronavirus in the world, even going back to the original outbreak, Sub-Saharan Africa is not a hotspot.

“It turns out though that when you look at some of the zero-prevalence studies that are coming out of Africa, and there’s actually something that’s in, the link was provided to Emily, but it’s over 70 percent of people have already been exposed or have evidence of infection in Africa. And just our experience doing clinical trials there on effectiveness trials, 90 to 95 percent of people in some areas have already been infected. So we missed the wave. We missed deaths. The countries didn’t realize there were waves so they really don’t necessarily think that that coronavirus is a real problem.

“What are the costs? So we don’t know the costs. We know the costs in the United States, we can probably calculate the costs in Europe where there was diagnosis, there were hospitalizations and costs were knowable. In countries where we didn’t, and we don’t have that information. We don’t have information on the cost of illness, we don’t know the broader costs. We know what lockdown costs, but if a parent is out, say a family is living on $1 to $2 a day, which is about the poverty level globally, they can’t work because they’re in lockdown, they’re in isolation or they can’t work because a child is sick.

“Families drop from $1 a day to $0 a day. It turns out that those families that are in poverty remain in poverty on the average for nine months. So the implication here is that it would be great if we could understand the true costs of infection and hospitalization or clinic visits, or time out for more for the broader economic costs. When a family drops under the poverty level, children have to work, they don’t go to school. They may not get vaccinated because health-care workers are busy taking care of other problems. And so the actual costs and the broader costs of not doing anything, we can’t estimate. And I think organizations around the world are trying to do that, and they can do the total economic impact — billions of dollars in a developing country is a huge amount of money. So again, I think it’s one of those things that we really desperately need answers because it’ll help justify the use of vaccine in low- and middle-income countries.”

Emily Underwood: “Thanks so much.”

Maria Elena Bottazzi: “And maybe, Emily, I was just going to add to the fact that you have to also put it in context that quantifying what the direct impact of the Covid-19 was, you have to also add all the indirect potential issues that it caused, right? So the amount of hours lost, of kids not have been able to go to school, the food insecurity, the fact that we probably went backwards in a lot of the millennium development goal achievements that we have had in the last 15, 20 years. The fact that we also stopped doing standard immunization campaigns for other diseases, right, that probably also brought in additional impact, not only to families, kids.

“So I think that it’s probably an enormous amount of economic health security, everything, right, that this Covid-19 have. And we don’t actually do not know how much longer this will also go forward because we’re starting to now seeing that there’s going to be such long-term sequelae from those who have, of course recovered from the disease. We don’t know how many of those are going to then have issues with health or productivity and so I think this is going to be for a long haul, unfortunately.”

Emily Underwood: “So you are in hotel rooms across the street from each other in DC, right, both of you at the World Vaccine Congress. With so many countries coming together to talk about this, I’m going to ask a question from Kavita Vedhara. She asks, ‘We know now that there are stark inequalities in Covid outcomes related to socioeconomic and ethnic factors in many high-income countries like the UK, despite this such countries have not done anything to put these groups at the front of the queue at home, what do you think this tells us about the willingness or ability of high-income countries to distribute vaccines in an equitable way?’ And I’m just personally curious, what is the mood or the hopes that you have for the conference that you’re at right now? What are you hoping to see come out of this meeting?”

Jerome Kim: “I think you should go first, Maria Elena.”

Maria Elena Bottazzi: “OK, sure. Sure. So traditionally, these meetings had always been industry-led. And I think for the last, maybe five, six years, slowly they have been seeing how inviting the academic side, the nonprofit organizations of certainly like IVI to also converse so that we all can learn from each other, share information amongst each other. We all have different business models, right? We all have a different role in the ecosystem of vaccine development, testing, commercializing, licensing, the access. So I think that it’s much more collegial and that we certainly can learn from each other.

“So my hope is to see that we can continue forging more and more these collaborations, but a word also of caution. And of course, that what I would like to see more is that it’s still a little bit skewed even within these types of congresses that it’s too much led by again, that high-income country and there’s not a lot of participation and diversity by bringing in also the, for example, developing country vaccine manufacturers or the clinical trial sites that actually do some of these clinical trials in those low-, middle-income country settings.

“I think we still have a ways to go, but that slowly we’re being more ourselves, more equitable, diverse, and the hope is that therefore it gives voices. It just enables to bring the voices from all over the world. So that’s my hope, but we’re still not there yet I think. I don’t know if you would agree with me, Jerome. It’s still a little bit skewed when we walk around the Marriott here in DC of who you see and who’s giving the talks.”

Jerome Kim:  “Yeah, it’s interesting. And I was on a panel yesterday, I was supposed to talk about some of these questions and it was very focused on the US. So the World Vaccine Congress, actually, there’s a US version and a European version. So I would guess that maybe it will get more of a European focus, but again, largely it’s industry-driven, this particular conference. But there were quite a few groups, not only ours, but the Saban Institute and PATH and other organizations, academics now represented as well. So they’re trying to incorporate more of the global health focus because really, vaccines are an essential tool.

“They’re something that high-income countries have had and use, and that low-income countries, and particularly the effective ones have really been at the forefront of ensuring that 90 percent of the population to be vaccinated in Thailand. So I think we recognize that, and I think that the question gets to a broader question about what we call trust and acceptance. Basically there was a year of people talking about how bad these vaccines were and going to be rushed into production. And then as countries were waiting to receive their vaccine, they got even more information about vaccine does this, there are microchips in them, all this misinformation. We didn’t do what we normally do.

“So when IVI is introducing, say cholera vaccine to a country that won’t admit that it has a case of cholera, it’ll only talk about ‘acute watery diarrhea.’ We go to them with the data. These are the data on cholera. This is the number of people who are put in the hospital. This is the cost, the burden to society of doing that, then this is how much the vaccine costs, $1.30 a dose. It costs 86 cents to administer because it’s oral. And so if you count the cost of the campaigns, et cetera, this is the total cost. This is how much you save in terms of total health-care costs.

“And the country will say, ‘OK, you’re right. We will prepare a national cholera eradication plan.’ Great. But you have to do that. And then as they’re rolling out vaccine, the countries, because they’re used to doing this, put into place a set of community engagement exercises. In high-income countries, we really didn’t see that. In some, so Native American populations, some tribes did a really great job of getting people vaccinated. But again, this is about going into communities, explaining, getting rid of or dispelling misinformation, using effective techniques to engage the population, get them to want to be vaccinated. And this is not something that, you know, we do particularly well in the United States.

“It is actually remarkable that 80 to 85 percent of American children receive all of 26 different injections for 14 different diseases their parents have never seen, but there’s a lot more resistance to Covid vaccination. And it’s actually now with all the misinformation it’s beginning to eat into and disrupt the consensus around giving children vaccines. So I think one of the things that we need to work on globally — not only in high-income countries, but everywhere — is to restore the consensus around the real benefits of vaccination. And unless we can do that, we’re going to undermine 20 years of progress in pediatric vaccination and the progress that’s now been made in life-course vaccination globally.”

Emily Underwood: “Thank you. I know we’re a couple minutes over. Would you guys be willing to answer just one more question from the audience? We have a lot of really good ones? OK. I’d just like to ask this question, which I think a lot of us are confused about and curious about, which is, how does the need for multiple boosters and boosters over the long term affect equity? Maria, do you want to take that first?”

Maria Elena Bottazzi: “ Yeah. Well, again, it is a pretty good question because as you stated at the beginning, we still have a lot of people who haven’t even received even their first vaccine schedule, right? Even the first two doses. So then the question is what do you prioritize, right? Do you prioritize sending vaccines to those populations who have not received any, do you then, of course, vaccinate again, the high-risk populations, who do you give your boosters first if you don’t have enough to, of course, to just boost absolutely everyone, how do you start integrating in again, pediatric vaccination? So it is a conundrum that again, countries are going to have to balance on the basis of how much vaccine can they afford and they can get access, and which of course, vaccine technology, eventually they can receive.

“Are they going to be able to do mix-match approaches, right? So if you already got a whole inactivated virus, can you boost with something else? So there’s a lot of still questions. And so countries need help with these types of decisions. And I think that’s, I know that we didn’t discuss this too much and maybe Jerome can comment about this notion that we’re hearing now that we have vaccine availability, but Africa right now is asking not to send it because they don’t have the systems to deploy them. And this additional capacity is that the countries are not prepared. And then on top of it, you have to, of course, superimpose of how do you do it in the context of the boosting strategy and the variants that are circulating? So it is a pretty complex question.

“So I know Jerome has probably a better answer that I have, of this absorption capacity, right? What do you do now, right, that you have all these vaccines, but you still have very complicated strategies of who do you give them to and how do you mix-match?”

Jerome Kim: “Yeah. And Maria Elena got to this point, which is supply is not the issue anymore. And the real question is vaccination. And remember, our old professors of medicine taught us vaccines don’t save lives, vaccination saves lives. And when we think that the world struggles, not struggles, but it’s hard to vaccinate 80 percent of the birth cohort — 80 to 85 percent of children receive all the EPI vaccines they’re supposed to get; that still leaves 13 million children who don’t see a vaccine. But roughly 80 to 85 percent of the 130 million births every year are fully covered by vaccination, which is great.

“But now imagine that we’re going to have to vaccinate 8 billion. And you get an idea that a health-care system that’s already under-resourced is going to have real problems — and this is called absorption capacity — with giving these vaccines. And so it’s really not only the logistic system, the cold chain, the disposal of syringes and vials, which actually weighs more than the weight of the vaccine doses. All of this is a problem. And then you’re going to health-care staff who are really overworked, they’re under-resourced. And now you’re going to say, ‘Well, not only you have to vaccinate the children, but vaccinate their brothers and sisters, mom and dad, and grandma and grandpa.’

“And you’ll get an idea that the amount of work that is going to be required is tremendous, and we haven’t spent time. If we put $20 billion into strengthening health-care systems around the world, we would not only be benefiting vaccination. We would be benefiting one of the sustainable development goals around providing health care to people around the world. So this really does get to a bigger problem that we have, which is giving vaccines and providing health care. And it’s one of those things we really need to focus on if we want to be able to deal with pandemics better in the future.”

Emily Underwood: “Well, thank you so much to both of you. I’m just so grateful to have had this time with you. It has been such a pleasure. You should know that I actually crawled through a window this morning to get to this conversation. I got locked out of my house and I crawled in through the window, and I’m just so glad that we made it and we’re all here. And I have enjoyed this so much, and I know that our audience has as well. Are there any final thoughts you want to share before we sign off? Maybe Jerome, go first.”

Jerome Kim: “OK. So we talked about the equity gaps, but we didn’t really put them all down. There was a vaccine supply equity gap; we’re now dealing with the vaccination equity gap. But the gap that we didn’t talk about at all is the diagnostics gap. Again, unless you know there’s a problem, you’re not going to be testing. If you’re not testing, you don’t know there’s a problem, which means that you don’t know how many deaths there are. And because we’re not sequencing, another of the equity gaps, we don’t know where the variants are. So we’re blind and we really don’t understand what we’re facing. And I think that as we bridge these things, we’re going to respond better in the future, assuming we can rebuild consensus around the global need and the importance of vaccination.”

Maria Elena Bottazzi: “And from my side, my final comments are, again, it’s the fact that if we really would like to arrive to really be equitable and achieve this world equity at all levels, everybody has to have the opportunity of having their own voice, and participating and contributing and being considered equal, right, in the contribution, especially during whether it’s science, vaccine development or strengthening. And that’s what we have strived for, is to invite everybody around that table to have these conversations, because, true, we may have some advantages in some regions of the world than others, but we all are human beings that are very capable to be creative, innovative and with the right resources and tools, and certainly political will and resources, we can really raise the entire world to protect everybody, and not have this skew that we all protect our regions and forget that if we don’t protect the rest of the world, we’re going to get out of these types of situations.

“So the hope is that in the future, we learn also to communicate better with each other and learn how to get rid of all the misinformation and disinformation and really extract out what’s real and what is trustworthy. And that’s why we appreciate all that Knowable Magazine does, and certainly Annual Reviews does, because like you said, we should all be smart, trustworthy and put out timely information, but that it also brings a compelling story. Thank you.”

Emily Underwood: “Well, thank you. Thank you so much for joining us, I hope the rest of the congress goes splendidly and that your travels are smooth. Thanks so much. I’d like to thank our audience today. I’d like to thank also the Alfred P. Sloan Foundation and the Gordon and Betty Moore Foundation for their wonderful support of Knowable Magazine. And this conversation, as a reminder, will be posted on the Knowable website. It’ll be free to view and share.

“Our additional resources and the links to the articles that we talked about will be there. And as a reminder, the best way to keep up with these discussions and everything Knowable is to sign up for our weekly newsletter, which you can do it on our website, knowablemagazine.org, or follow on Twitter @KnowableMag. We will see you again at our next event, on June 29th. Again, that will be about the origins of the Grand Canyon. And thank you again for joining us.”