Can an “old school” vaccine address global inequities in Covid-19 vaccination?
When the COVID-19 pandemic began invading the world in late 2019, Peter Hotez and Maria Elena Bottazzi set out to create a low-cost vaccine that would help inoculate populations in low- and middle-income countries. The scientists, with their prior experience of developing inexpensive vaccines for the world’s poor, had anticipated that the global rollout of Covid-19 jabs would be marked with several inequities. They wanted to create a patent-free vaccine to bridge this gap, but the U.S. government did not seem impressed, forcing the researchers to turn to private philanthropies for funds.
Hotez and Bottazzi, both scientists at the Texas Children’s Hospital Center for Vaccine Development at Baylor College of Medicine, raised about $9 million in private funds. Meanwhile, the U.S. government’s contribution stood at $400,000.
“That was a very tough time early on in the pandemic, you know, trying to do the work and raise the money for it at the same time,” says Hotez, who was nominated in February for a Nobel Peace Prize with Bottazzi for their COVID-19 vaccine. He adds that at the beginning of the pandemic, governments emphasized speed, innovation and rapidly immunizing populations in North America and Europe with little consideration for poorer countries. “We knew this [vaccine] was going to be the answer to global vaccine inequality, but I just wish the policymakers had felt the same,” says Hotez.
Over the past two years, the world has witnessed 488 million COVID-19 infections and over 61 million deaths. Over 11 billion vaccine doses have been administered worldwide; however, the global rollout of COVID-19 vaccines is marked with alarming socio-economic inequities. For instance, 72 percent of the population in high-income countries has received at least one dose of the vaccine, whereas the number stands at 15 percent in low-income countries.
This inequity is worsening vulnerabilities across the world, says Lawrence Young, a virologist and co-lead of the Warwick Health Global Research Priority at the UK-based University of Warwick. “As long as the virus continues to spread and replicate, particularly in populations who are under-vaccinated, it will throw up new variants and these will remain a continual threat even to those countries with high rates of vaccination,” says Young, “Therefore, it is in all our interests to ensure that vaccines are distributed equitably across the world.”
“When your house is on fire, you don't call the patent attorney,” says Hotez. “We wanted to be the fire department.”
The vaccine developed by Hotez and Bottazzi recently received emergency use authorisation in India, which plans to manufacture 100 million doses every month. Dubbed ‘Corbevax’ by its Indian maker, Biological E Limited, the vaccine is now being administered in India to children aged 12-14. The patent-free arrangement means that other low- and middle-income countries could also produce and distribute the vaccine locally.
“When your house is on fire, you don't call the patent attorney, you call the fire department,” says Hotez, commenting on the intellectual property rights waiver. “We wanted to be the fire department.”
The Inequity
Vaccine equity simply means that all people, irrespective of their location, should have equal access to vaccines. However, data suggests that the global COVID-19 vaccine rollout has favoured those in richer countries. For instance, high-income countries like the UAE, Portugal, Chile, Singapore, Australia, Malta, Hong Kong and Canada have partially vaccinated over 85 percent of their populations. This percentage in poorer countries, meanwhile, is abysmally low – 2.1 percent in Yemen, 4.6 in South Sudan, 5 in Cameroon, 9.9 in Burkina Faso, 10 in Nigeria, 12 in Somalia, 12 in Congo, 13 in Afghanistan and 21 in Ethiopia.
In late 2019, scientists Peter Hotez and Maria Elena Bottazzi set out to create a low-cost vaccine that would help inoculate populations in low- and middle-income countries. In February, they were nominated for a Nobel Peace Prize.
Texas Children's Hospital
The COVID-19 vaccination coverage is particularly low in African countries, and according to Shabir Madhi, a vaccinologist at the University of the Witwatersrand, Johannesburg and co-director of African Local Initiative for Vaccinology Expertise, vaccine access and inequity remains a challenge in Africa. Madhi adds that a lack of vaccine access has affected the pandemic’s trajectory on the continent, but a majority of its people have now developed immunity through natural infection. “This has come at a high cost of loss of lives,” he says.
COVID-19 vaccines mean a significant financial burden for poorer countries, which spend an average of $41 per capita annually on health, while the average cost of every COVID-19 vaccine dose ranges between $2 and $40 in addition to a distribution cost of $3.70 per person for two doses. In December last year, the World Health Organisation (WHO) set a goal of immunizing 70 percent of the population of all countries by mid-2022. This, however, means that low-income countries would have to increase their health expenditure by an average of 56.6 percent to cover the cost, as opposed to 0.8 per cent in high-income countries.
Reflecting on the factors that have driven global inequity in COVID-19 vaccine distribution, Andrea Taylor, assistant director of programs at the Duke Global Health Innovation Center, says that wealthy nations took the risk of investing heavily in the development and scaling up of COVID-19 vaccines – at a time when there was little evidence to show that vaccines would work. This reserved a place for these nations at the front of the queue when doses started rolling off production lines. Lower-income countries, meanwhile, could not afford such investments.
“Now, however, global supply is not the issue,” says Taylor. “We are making plenty of doses to meet global need. The main problem is infrastructure to get the vaccine where it is most needed in a predictable and timely way and to ensure that countries have all the support they need to store, transport, and use the vaccine once it is received.”
Taufique Joarder, vice-chairperson of Bangladesh's Public Health Foundation, sees the need for more trials and data before Corbevax is made available to the general population.
In addition to global inequities in vaccination coverage, there are inequities within nations. Taufique Joarder, vice-chairperson of Bangladesh’s Public Health Foundation, points to the situation in his country, where vaccination coverage in rural and economically disadvantaged communities has suffered owing to weak vaccine-promotion initiatives and the difficulty many people face in registering online for jabs.
Joarder also cites the example of the COVID-19 immunization drive for children aged 12 years and above. “[Children] are given the Pfizer vaccine, which requires an ultralow temperature for storage. This is almost impossible to administer in many parts of the country, especially the rural areas. So, a large proportion of the children are being left out of vaccination,” says Joarder, adding that Corbevax, which is cheaper and requires regular temperature refrigeration “can be an excellent alternative to Pfizer for vaccinating rural children.”
Corbevax vs. mRNA Vaccines
As opposed to most other COVID-19 vaccines, which use the new Messenger RNA (mRNA) vaccine technology, Corbevax is an “old school” vaccine, says Hotez. The vaccine is made through microbial fermentation in yeast, similar to the process used to produce the recombinant hepatitis B vaccine, which has been administered to children in several countries for decades. Hence, says Hotez, the technology to produce Corbevax at large scales is already in place in countries like Vietnam, Bangladesh, India, Indonesia, Brazil, Argentina, among many others.
“So if you want to rapidly develop and produce and empower low- and middle-income countries, this is the technology to do it,” he says.
“Global access to high-quality vaccines will require serious investment in other types of COVID-19 vaccines," says Andrea Taylor.
The COVID-19 vaccines created by Pfizer-BioNTech and Moderna marked the first time that mRNA vaccine technology was approved for use. However, scientists like Young feel that there is “a need to be pragmatic and not seduced by new technologies when older, tried and tested approaches can also be effective.” Taylor, meanwhile, says that although mRNA vaccines have dominated the COVID-19 vaccine market in the U.S., “there is no clear grounding for this preference in the data we have so far.” She adds that there is also growing evidence that the immunity from these shots may not hold up as well over time as that of vaccines using different platforms.
“The mRNA vaccines are well suited to wealthy countries with sufficient ultra-cold storage and transportation infrastructure, but these vaccines are divas and do not travel well in the rest of the world,” says Taylor. “Global access to high-quality vaccines will require serious investment in other types of COVID-19 vaccines, such as the protein subunit platform used by Novavax and Corbevax. These require only standard refrigeration, can be manufactured using existing facilities all over the world, and are easy to transport.”
Joarder adds that Corbevax is cheaper due to the developers’ waived intellectual rights. It could also be used as a booster vaccine in Bangladesh, where only five per cent of the population has currently received booster doses. “If this vaccine is proved effective for heterologous boosting, [meaning] it works well and is well tolerated as a booster with other vaccines that are available in Bangladesh, this can be useful,” says Joarder.
According to Hotez, Corbevax can play several important roles - as a standalone adult or paediatric vaccine, and as a booster for other vaccines. Studies are underway to determine Corbevax’s effectiveness in these regards, he says.
Need for More Data
Biological E conducted two clinical trials involving 3000 subjects in India, and found Corbevax to be “safe and immunogenic,” with 90 percent effectiveness in preventing symptomatic infections from the original strain of COVID-19 and over 80 percent effectiveness against the Delta variant. The vaccine is currently in use in India, and according to Hotez, it’s in the pipeline at different stages in Indonesia, Bangladesh and Botswana.
However, Corbevax is yet to receive emergency use approval from the WHO. Experts such as Joarder see the need for more trials and data before it is made available to the general population. He says that while the WHO’s emergency approval is essential for global scale-up of the vaccine, we need data to determine age-stratified efficacy of the vaccine and whether it can be used for heterologous boosting with other vaccines. “According to the most recent data, the 100 percent circulating variant in Bangladesh is Omicron. We need to know how effective is Corbevax against the Omicron variant,” says Joarder.
Shabir Madhi, a vaccinologist at the University of the Witwatersrand, Johannesburg and co-director of the African Local Initiative for Vaccinology Expertise, says that a majority of people in Africa have now developed immunity through natural infection. “This has come at a high cost of loss of lives."
Shivan Parusnath
Others, meanwhile, believe that availing vaccines to poorer countries is not enough to resolve the inequity. Young, the Warwick virologist, says that the global vaccination rollout has also suffered from a degree of vaccine hesitancy, echoing similar observations by President Biden and Pfizer’s CEO. The problem can be blamed on poor communication about the benefits of vaccination. “The Corbevax vaccine [helps with the issues of] patent protection, vaccine storage and distribution, but governments need to ensure that their people are clearly informed.” Notably, however, some research has found higher vaccine willingness in lower-income countries than in the U.S.
Young also emphasized the importance of establishing local vaccination stations to improve access. For some countries, meanwhile, it may be too late. Speaking about the African continent, Madhi says that Corbevax has arrived following the peak of the crisis and won’t reverse the suffering and death that has transpired because of vaccine hoarding by high-income countries.
“The same goes for all the sudden donations from countries such as France - pretty much of little to no value when the pandemic is at its tail end,” says Madhi. “This, unfortunately, is a repeat of the swine flu pandemic in 2009, when vaccines only became available to Africa after the pandemic had very much subsided.”
Your phone could show if a bridge is about to collapse
In summer 2017, Thomas Matarazzo, then a postdoctoral researcher at the Massachusetts Institute of Technology, landed in San Francisco with a colleague. They rented two cars, drove up to the Golden Gate bridge, timing it to the city’s rush hour, and rode over to the other side in heavy traffic. Once they reached the other end, they turned around and did it again. And again. And again.
“I drove over that bridge 100 times over five days, back and forth,” says Matarazzo, now an associate director of High-Performance Computing in the Center for Innovation in Engineering at the United States Military Academy, West Point. “It was surprisingly stressful, I never anticipated that. I had to maintain the speed of about 30 miles an hour when the speed limit is 45. I felt bad for everybody behind me.”
Matarazzo had to drive slowly because the quality of data they were collecting depended on it. The pair was designing and testing a new smartphone app that could gather data about the bridge’s structural integrity—a low-cost citizen-scientist alternative to the current industrial methods, which aren’t always possible, partly because they’re expensive and complex. In the era of aging infrastructure, when some bridges in the United States and other countries are structurally unsound to the point of collapsing, such an app could inform authorities about the need for urgent repairs, or at least prompt closing the most dangerous structures.
There are 619,588 bridges in the U.S., and some of them are very old. For example, the Benjamin Franklin Bridge connecting Philadelphia to Camden, N.J., is 96-years-old while the Brooklyn Bridge is 153. So it’s hardly surprising that many could use some upgrades. “In the U.S., a lot of them were built in the post-World War II period to accommodate the surge of motorization,” says Carlo Ratti, architect and engineer who directs the Senseable City Lab at Massachusetts Institute of Technology. “They are beginning to reach the end of their life.”
According to the 2022 American Road & Transportation Builders Association’s report, one in three U.S. bridges needs repair or replacement. The Department of Transportation (DOT) National Bridge Inventory (NBI) database reveals concerning numbers. Thirty-six percent of U.S. bridges need repair work and over 78,000 bridges should be replaced. More than 43,500 bridges are rated in poor condition and classified as “structurally deficient” – an alarming description. Yet, people drive over them 167.5 million times a day. The Pittsburgh bridge which collapsed in January this year—only hours before President Biden arrived to discuss the new infrastructure law—was on the “poor” rating list.
Assessing the structural integrity of a bridge is not an easy endeavor. Most of the time, these are visual inspections, Matarazzo explains. Engineers check cracks, rust and other signs of wear and tear. They also check for wildlife—birds which may build nests or even small animals that make homes inside the bridge structures, which can slowly chip at the structure. However, visual inspections may not tell the whole story. A more sophisticated and significantly more expensive inspection requires placing special sensors on the bridge that essentially listen to how the bridge vibrates.
“Some bridges can afford expensive sensors to do the job, but that comes at a very high cost—hundreds of thousands of dollars per bridge per year,” Ratti says.
We may think of bridges as immovable steel and concrete monoliths, but they naturally vibrate, oscillating slightly. That movement can be influenced by the traffic that passes over them, and even by wind. Bridges of different types vibrate differently—some have longer vibrational frequencies and others shorter ones. A good way to visualize this phenomenon is to place a ruler over the edge of a desk and flick it slightly. If the ruler protrudes far off the desk, it will vibrate slowly. But if you shorten the end that hangs off, it will vibrate much faster. It works similarly with bridges, except there are more factors at play, including not only the length, but also the design and the materials used.
The long suspension bridges such as the Golden Gate or Verrazano Narrows, which hang on a series of cables, are more flexible, and their vibration amplitudes are longer. The Golden Gate Bridge can vibrate at 0.106 Hertz, where one Hertz is one oscillation per second. “Think about standing on the bridge for about 10 seconds—that's how long it takes for it to move all the way up and all the way down in one oscillation,” Matarazzo says.
On the contrary, the concrete span bridges that rest on multiple columns like Brooklyn Bridge or Manhattan Bridge, are “stiffer” and have greater vibrational frequencies. A concrete bridge can have a frequency of 10 Hertz, moving 10 times in one second—like that shorter stretch of a ruler.
The special devices that can pick up and record these vibrations over time are called accelerometers. A network of these devices for each bridge can cost $20,000 to $50,000, and more—and require trained personnel to place them. The sensors also must stay on the bridge for some time to establish what’s a healthy vibrational baseline for a given bridge. Maintaining them adds to the cost. “Some bridges can afford expensive sensors to do the job, but that comes at a very high cost—hundreds of thousands of dollars per bridge per year,” Ratti says.
Making sense of the readouts they gather is another challenge, which requires a high level of technical expertise. “You generally need somebody, some type of expert capable of doing the analysis to translate that data into information,” says Matarazzo, which ticks up the price, so doing visual inspections often proves to be a more economical choice for state-level DOTs with tight budgets. “The existing systems work well, but have downsides,” Ratti says. The team thought the old method could use some modernizing.
Smartphones, which are carried by millions of people, contain dozens of sensors, including the accelerometers capable of picking up the bridges’ vibrations. That’s why Matarazzo and his colleague drove over the bridge 100 times—they were trying to pick up enough data. Timing it to rush hour supported that goal because traffic caused more “excitation,” Matarazzo explains. “Excitation is a big word we use when we talk about what drives the vibration,” he says. “When there's a lot of traffic, there's more excitation and more vibration.” They also collaborated with Uber, whose drivers made 72 trips across the bridge to gather data in different cars.
The next step was to clean the data from “noise”—various vibrations that weren’t relevant to the bridge but came from the cars themselves. “It could be jumps in speed, it could be potholes, it could be a bunch of other things," Matarazzo says. But as the team gathered more data, it became easier to tell the bridge vibrational frequencies from all others because the noises generated by cars, traffic and other things tend to “cancel out.”
The team specifically picked the Golden Gate bridge because the civil structural engineering community had studied it extensively over the years and collected a host of vibrational data, using traditional sensors. When the researchers compared their app-collected frequencies with those gathered by 240 accelerometers formerly placed on the Golden Gate, the results were the same—the data from the phones converged with that from the bridge’s sensors. The smartphone-collected data were just as good as those from industry devices.
The study authors estimate that officials could use crowdsourced data to make key improvements that would help new bridges to last about 14 years longer.
The team also tested their method on a different type of bridge—not a suspension one like the Golden Gate, but a concrete span bridge in Ciampino, Italy. There they compared 280 car trips over the bridge to the six sensors that had been placed on the bridge for seven months. The results were slightly less matching, but a larger volume of trips would fix the divergence, the researchers wrote in their study, titled Crowdsourcing bridge dynamic monitoring with smartphone vehicle trips, published last month in Nature Communications Engineering.
Although the smartphones proved effective, the app is not quite ready to be rolled out commercially for people to start using. “It is still a pilot version,” so there’s room for improvement, says Ratti, who co-authored the study. “But on a more optimistic note, it has really low barriers to entry—all you need is smartphones on cars—so that makes the system easy to reach a global audience.” And the study authors estimate that the use of crowdsourced data would result in a new bridge lasting about 14 years longer.
Matarazzo hopes that the app could be eventually accessible for your average citizen scientist to collect the data and supply it to their local transportation authorities. “I hope that this idea can spark a different type of relationship with infrastructure where people think about the data they're collecting as some type of contribution or investment into their communities,” he says. “So that they can help their own department of transportation, their own municipality to support that bridge and keep it maintained better, longer and safer.”
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.
The Friday Five: Sugar could help catch cancer early
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
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Here are the promising studies covered in this week's Friday Five:
- Catching cancer early could depend on sugar
- How to boost memory in a flash
- This is your brain on books
- A tiny sandwich cake could help the heart
- Meet the top banana for fighting Covid variants