Scientists at Baylor College of Medicine developed a vaccine called Corbevax that, unlike mRNA vaccines, can be mass produced using technology already in place in low- and middle-income countries. It's now being administered in India to children aged 12-14.
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 larvae of adult black soldier flies can turn food waste into sustainable protein with minimal methane gas emissions.
Their capacity to consume presents a neat response to the problem of food waste, which contributes up to 8% of global greenhouse gas emissions each year as it rots in landfill.
"The maggots eat the food fairly fresh," Gordon says. "So, there's minimal degradation and you don't get those methane emissions."
Alongside their ability to devour waste, the soldier fly larvae hold further agricultural promise: they yield an incredibly efficient protein. After the maggots have binged for about 12 days, Goterra harvests and processes them into a protein-rich livestock feed. Their excrement, known as frass, is also collected and turned into soil conditioner.
"We are producing protein in a basement," says Gordon. "It's urban farming – really sustainable, urban farming."
Goterra's module in the basement at Barangaroo, Sydney.
Supplied by Goterra
Goterra's founder Olympia Yarger started producing the insects in "buckets in her backyard" in 2016. Today, Goterra has a large-scale processing plant and has developed proprietary modules – in shipping containers – that use robotics to manage the larvae.
The modules have been installed on site at municipal buildings, hospitals, supermarkets, several McDonald's restaurants, and a range of smaller enterprises in Australia. Users pay a subscription fee and simply pour in the waste; Goterra visits once a fortnight to harvest the bugs.
Insect agriculture is well established outside of the West, and the practice is gaining traction around the world. China has mega-facilities that can process hundreds of tons of waste in a day. In Kenya, a program recently trained 2000 farmers in soldier fly farming to boost their economic security. French biotech company InnovaFeed, in partnership with US agricultural heavyweight ADM, plans to build "the world's largest insect protein facility" in Illinois this year.
"The [maggots] are science fiction on earth. Watching them work is awe-inspiring."
But the concept is still not to everyone's taste.
"This is still a topic that I say is a bit like black liquorice – people tend to either really like it or really don't," says Wendy Lu McGill, Communications Director at the North American Coalition of Insect Agriculture (NACIA).
Formed in 2016, NACIA now has over 100 members – including researchers and commercial producers of black soldier flies, meal worms and crickets.
McGill says there have been a few iterations of insect agriculture in the US – beginning with worms produced for bait after World War II then shifting to food for exotic pets. The current focus – "insects as food and feed" – took root about a decade ago, with the establishment of the first commercial farms for this purpose.
"We're starting to see more expansion in the U.S. and a lot of the larger investments have been for black soldier fly producers," McGill says. "They tend to have larger facilities and the animal feed market they're looking at is potentially quite large."
InnovaFeed's Illinois facility is set to produce 60,000 metric tons of animal feed protein per year.
"They'll be trying to employ many different circular principles," McGill says of the project. "For example, the heat from the feed factory – the excess heat that would normally just be vented – will be used to heat the other side that's raising the black soldier fly."
Although commercial applications have started to flourish recently, scientific knowledge of the black soldier fly's potential has existed for decades.
Dr. Jeffery Tomberlin, an entomologist at Texas A&M University, has been studying the insect for over 20 years, contributing to key technologies used in the industry. He also founded Evo, a black soldier fly company in Texas, which feeds its larvae the waste from a local bakery and distillery.
"They are science fiction on earth," he says of the maggots. "Watching them work is awe-inspiring."
Tomberlin says fly farms can work effectively at different scales, and present possibilities for non-Western countries to shift towards "commodity independence."
"You don't have to have millions of dollars invested to be successful in producing this insect," he says. "[A farm] can be as simple as an open barn along the equator to a 30,000 square-foot indoor facility in the Netherlands."
As the world's population balloons, food insecurity is an increasing concern. By 2050, the UN predicts that to feed our projected population we will need to ramp up food production by at least 60%. Insect agriculture, which uses very little land and water compared to traditional livestock farming, could play a key role.
Insects may become more common human food, but the current commercial focus is animal feed. Aquaculture is a key market, with insects presenting an alternative to fish meal derived from over-exploited stocks. Insect meal is also increasingly popular in pet food, particularly in Europe.
While recent investment has been strong – NACIA says 2020 was the best year yet – reaching a scale that can match existing agricultural industries and providing a competitive price point are still hurdles for insect agriculture.
But COVID-19 has strengthened the argument for new agricultural approaches, such as the decentralized, indoor systems and circular principles employed by insect farms.
"This has given the world a preview – which no one wanted – of [future] supply chain disruptions," says McGill.
As the industry works to meet demand, Tomberlin predicts diversification and product innovation: "I think food science is going to play a big part in that. They can take an insect and create ice cream." (Dried soldier fly larvae "taste kind of like popcorn," if you were wondering.)
Tomberlin says the insects could even become an interplanetary protein source: "I do believe in that. I mean, if we're going to colonize other planets, we need to be sustainable."
But he issues a word of caution about the industry growing too big, too fast: "I think we as an industry need to be very careful of how we harness and apply [our knowledge]. The black soldier fly is considered the crown jewel today, but if it's mismanaged, it can be relegated back to a past."
Goterra's Gordon also warns against rushing into mass production: "If you're just replacing big intensive animal agriculture with big intensive animal agriculture with more efficient animals, then what's the change you're really effecting?"
But he expects the industry will continue its rise though the next decade, and Goterra – fuelled by recent $8 million Series A funding – plans to expand internationally this year.
"Within 10 years' time, I would like to see the vast majority of our unavoidable food waste being used to produce maggots to go into a protein application," Gordon says.
"There's no lack of demand. And there's no lack of food waste."