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.”
The Friday Five: A surprising health benefit for people who have kids
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:
- Kids stressing you out? They could be protecting your health.
- A new device unlocks the heart's secrets
- Super-ager gene transplants
- Surgeons could 3D print your organs before operations
- A skull cap looks into the brain like an fMRI
Can tech help prevent the insect apocalypse?
This article originally appeared in One Health/One Planet, a single-issue magazine that explores how climate change and other environmental shifts are making us more vulnerable to infectious diseases by land and by sea - and how scientists are working on solutions.
On a warm summer day, forests, meadows, and riverbanks should be abuzz with insects—from butterflies to beetles and bees. But bugs aren’t as abundant as they used to be, and that’s not a plus for people and the planet, scientists say. The declining numbers of insects, coupled with climate change, can have devastating effects for people in more ways than one. “Insects have been around for a very long time and can live well without humans, but humans cannot live without insects and the many services they provide to us,” says Philipp Lehmann, a researcher in the Department of Zoology at Stockholm University in Sweden. Their decline is not just bad, Lehmann adds. “It’s devastating news for humans.
”Insects and other invertebrates are the most diverse organisms on the planet. They fill most niches in terrestrial and aquatic environments and drive ecosystem functions. Many insects are also economically vital because they pollinate crops that humans depend on for food, including cereals, vegetables, fruits, and nuts. A paper published in PNAS notes that insects alone are worth more than $70 billion a year to the U.S. economy. In places where pollinators like honeybees are in decline, farmers now buy them from rearing facilities at steep prices rather than relying on “Mother Nature.”
And because many insects serve as food for other species—bats, birds and freshwater fish—they’re an integral part of the ecosystem’s food chain. “If you like to eat good food, you should thank an insect,” says Scott Hoffman Black, an ecologist and executive director of the Xerces Society for Invertebrate Conservation in Portland, Oregon. “And if you like birds in your trees and fish in your streams, you should be concerned with insect conservation.”
Deforestation, urbanization, and agricultural spread have eaten away at large swaths of insect habitat. The increasingly poorly controlled use of insecticides, which harms unintended species, and the proliferation of invasive insect species that disrupt native ecosystems compound the problem.
“There is not a single reason why insects are in decline,” says Jessica L. Ware, associate curator in the Division of Invertebrate Zoology at the American Museum of Natural History in New York, and president of the Entomological Society of America. “There are over one million described insect species, occupying different niches and responding to environmental stressors in different ways.”
Jessica Ware, an entomologist at the American Museum of Natural History, is using DNA methods to monitor insects.
Credit:D.Finnin/AMNH
In addition to habitat loss fueling the decline in insect populations, the other “major drivers” Ware identified are invasive species, climate change, pollution, and fluctuating levels of nitrogen, which play a major role in the lifecycle of plants, some of which serve as insect habitants and others as their food. “The causes of world insect population declines are, unfortunately, very easy to link to human activities,” Lehmann says.
Climate change will undoubtedly make the problem worse. “As temperatures start to rise, it can essentially make it too hot for some insects to survive,” says Emily McDermott, an assistant professor in the Department of Entomology and Plant Pathology at the University of Arkansas. “Conversely in other areas, it could potentially also allow other insects to expand their ranges.”
Without Pollinators Humans Will Starve
We may not think much of our planet’s getting warmer by only one degree Celsius, but it can spell catastrophe for many insects, plants, and animals, because it’s often accompanied by less rainfall. “Changes in precipitation patterns will have cascading consequences across the tree of life,” says David Wagner, a professor of ecology and evolutionary biology at the University of Connecticut. Insects, in particular, are “very vulnerable” because “they’re small and susceptible to drying.”
For instance, droughts have put the monarch butterfly at risk of being unable to find nectar to “recharge its engine” as it migrates from Canada and New England to Mexico for winter, where it enters a hibernation state until it journeys back in the spring. “The monarch is an iconic and a much-loved insect,” whose migration “is imperiled by climate change,” Wagner says.
Warming and drying trends in the Western United States are perhaps having an even more severe impact on insects than in the eastern region. As a result, “we are seeing fewer individual butterflies per year,” says Matt Forister, a professor of insect ecology at the University of Nevada, Reno.
There are hundreds of butterfly species in the United States and thousands in the world. They are pollinators and can serve as good indicators of other species’ health. “Although butterflies are only one group among many important pollinators, in general we assume that what’s bad for butterflies is probably bad for other insects,” says Forister, whose research focuses on butterflies. Climate change and habitat destruction are wreaking havoc on butterflies as well as plants, leading to a further indirect effect on caterpillars and butterflies.
Different insect species have different levels of sensitivity to environmental changes. For example, one-half of the bumblebee species in the United States are showing declines, whereas the other half are not, says Christina Grozinger, a professor of entomology at the Pennsylvania State University. Some species of bumble bees are even increasing in their range, seemingly resilient to environmental changes. But other pollinators are dwindling to the point that farmers have to buy from the rearing facilities, which is the case for the California almond industry. “This is a massive cost to the farmer, which could be provided for free, in case the local habitats supported these pollinators,” Lehmann says.
For bees and other insects, climate change can harm the plants they depend on for survival or have a negative impact on the insects directly. Overly rainy and hot conditions may limit flowering in plants or reduce the ability of a pollinator to forage and feed, which then decreases their reproductive success, resulting in dwindling populations, Grozinger explains.
“Nutritional deprivation can also make pollinators more sensitive to viruses and parasites and therefore cause disease spread,” she says. “There are many ways that climate change can reduce our pollinator populations and make it more difficult to grow the many fruit, vegetable and nut crops that depend on pollinators.”
Disease-Causing Insects Can Bring More Outbreaks
While some much-needed insects are declining, certain disease-causing species may be spreading and proliferating, which is another reason for human concern. Many mosquito types spread malaria, Zika virus, West Nile virus, and a brain infection called equine encephalitis, along with other diseases as well as heartworms in dogs, says Michael Sabourin, president of the Vermont Entomological Society. An animal health specialist for the state, Sabourin conducts vector surveys that identify ticks and mosquitoes.
Scientists refer to disease-carrying insects as vector species and, while there’s a limited number of them, many of these infections can be deadly. Fleas were a well-known vector for the bubonic plague, while kissing bugs are a vector for Chagas disease, a potentially life-threatening parasitic illness in humans, dogs, and other mammals, Sabourin says.
As the planet heats up, some of the creepy crawlers are able to survive milder winters or move up north. Warmer temperatures and a shorter snow season have spawned an increasing abundance of ticks in Maine, including the blacklegged tick (Ixodes scapularis), known to transmit Lyme disease, says Sean Birkel, an assistant professor in the Climate Change Institute and Cooperative Extension at the University of Maine.
Coupled with more frequent and heavier precipitation, rising temperatures bring a longer warm season that can also lead to a longer period of mosquito activity. “While other factors may be at play, climate change affects important underlying conditions that can, in turn, facilitate the spread of vector-borne disease,” Birkel says.
For example, if mosquitoes are finding fewer of their preferred food sources, they may bite humans more. Both male and female mosquitoes feed on sugar as part of their normal behavior, but if they aren’t eating their fill, they may become more bloodthirsty. One recent paper found that sugar-deprived Anopheles gambiae females go for larger blood meals to stay in good health and lay eggs. “More blood meals equals more chances to pick up and transmit a pathogen,” McDermott says, He adds that climate change could reduce the number of available plants to feed on. And while most mosquitoes are “generalist sugar-feeders” meaning that they will likely find alternatives, losing their favorite plants can make them hungrier for blood.
Similar to the effect of losing plants, mosquitoes may get turned onto people if they lose their favorite animal species. For example, some studies found that Culex pipiens mosquitoes that transmit the West Nile virus feed primarily on birds in summer. But that changes in the fall, at least in some places. Because there are fewer birds around, C. pipiens switch to mammals, including humans. And if some disease-carrying insect species proliferate or increase their ranges, that increases chances for human infection, says McDermott. “A larger concern is that climate change could increase vector population sizes, making it more likely that people or animals would be bitten by an infected insect.”
Science Can Help Bring Back the Buzz
To help friendly insects thrive and keep the foes in check, scientists need better ways of trapping, counting, and monitoring insects. It’s not an easy job, but artificial intelligence and molecular methods can help. Ware’s lab uses various environmental DNA methods to monitor freshwater habitats. Molecular technologies hold much promise. The so-called DNA barcodes, in which species are identified using a short string of their genes, can now be used to identify birds, bees, moths and other creatures, and should be used on a larger scale, says Wagner, the University of Connecticut professor. “One day, something akin to Star Trek’s tricorder will soon be on sale down at the local science store.”
Scientists are also deploying artificial intelligence, or AI, to identify insects in agricultural systems and north latitudes where there are fewer bugs, Wagner says. For instance, some automated traps already use the wingbeat frequencies of mosquitoes to distinguish the harmless ones from the disease-carriers. But new technology and software are needed to further expand detection based on vision, sound, and odors.
“Because of their ubiquity, enormity of numbers, and seemingly boundless diversity, we desperately need to develop molecular and AI technologies that will allow us to automate sampling and identification,” says Wagner. “That would accelerate our ability to track insect populations, alert us to the presence of new disease vectors, exotic pest introductions, and unexpected declines.”