Can an “old school” vaccine address global inequities in Covid-19 vaccination?

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.

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.”

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.

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.”