How do we vaccinate the world?

Much as isolated Australians might like to pretend otherwise, COVID-19 continues to fill mortuaries across the world. The global death toll has been mammoth, and it might be far greater than what we think.

Ultimately, our only way out of the pandemic is global vaccination. But vaccinating the whole world’s population has proven to be a huge effort, and the global need for vaccines might be far greater than we thought. Emerging variants continue to threaten vaccines’ efficacy, creating the possibility of dramatically increased demand for booster shots and reformulated vaccines.

So far, 1.5 billion vaccine doses have been administered across the world. But the distribution has been unequal and unfair. While the US has started vaccinating children, who have a minuscule risk of dying from COVID-19, African and South-East Asian countries are struggling to protect their elderly and frontline workers.

“It’s unethical,” says Professor Fiona Russell, a paediatrician at the Murdoch Children’s Research Institute, Melbourne, and expert in public health and epidemiology. “It’s a global pandemic, and the only way out is if every adult in every country is vaccinated.

“What happens in the rest of the world affects us directly. It’s in the best interest of every country to get the pandemic under control in all parts of the world.”

Last week The Economist published an estimate of the actual death toll from COVID-19, calculated with a machine-learning model. The model suggested that about 7–12 million more people have died from COVID-19 than have been reported.

While death rates in many high-income countries have run to tens or even hundreds of thousands, according to the model the overwhelming majority of the uncounted deaths were in low- and middle-income countries. Deaths for COVID-19 in Romania and Iran were more than double the official numbers. In Egypt, 13 times more people than reported died. In the US, the discrepancy was only 7.1%.

Now, a new COVID wave is striking through South-East Asia, and countries that got off relatively lightly last year, such as PNG and Timor Leste, have seen dangerous rises in case numbers.

More infectious variants have arisen, spreading fast, overwhelming healthcare systems and killing millions – even if the underlying virus is no more deadly.

Rich countries have made considerable investments in vaccine development and have committed to giving lavish sums of money to COVAX, the global collaboration that aims to ensure equitable vaccine distribution across the world.

But “it’s no matter of money,” says Professor Mike Toole, an epidemiologist at the Burnet Institute, Melbourne, and international public health expert. The issue, he says, is ramping up vaccine production and distribution.

Last October, India, South Africa, and 100 other countries put a resolution to the World Trade Organization (WTO) to introduce compulsory licensing for COVID-19 vaccines, therapeutics and diagnostics. Waiving vaccine patents means that more manufacturers could copy existing vaccines.

Under the WTO rules, any new therapeutic product, including vaccines, is entitled to have an exclusive patent for a number of years. A patent is a way to protect intellectual property, prohibiting any manufacturer that does not possess a license from producing that product. This protection allows drug developers to make profits and encourages investments in technological development.

About 20 years ago, the WTO introduced a Trade-Related Intellectual Property Rights (TRIPS) waiver that allowed compulsory licensing during public health emergencies.

Back then, the TRIPS waiver agreement was achieved to suspend intellectual property rights on HIV drugs because it was clear that African countries, which were the most affected by the HIV pandemic, could not afford the available medicines.

Consequently, many companies, mainly in India, began to produce generic versions of the HIV drugs at a much lower price than the original products. 

“That saved millions of lives, mainly in Africa,” Toole says. But the process to enable compulsory licensing dragged for years, and all the while millions died.

Now, the part of the world left behind in the race to COVID immunisation is calling for a TRIPS waiver on COVID-19 vaccines. The caveat, says Toole, is that some of the new, technologically advanced vaccines, such as the mRNA vaccines, are more complex to make than HIV drugs.

“There’s nothing particularly complicated in producing pills,” he says. “You just need the formula of the drug. But that’s not the case for vaccines.”

Professor David Legge, a public health scholar emeritus at La Trobe University, Melbourne, broadly agrees. “The waiver is not the be-all and end-all,” he says, pointing out that the cost of setting up new production lines and the need for technology transfer is not trivial.

The Pfizer and Moderna vaccines most nations long for are based on a brand-new technology for which manufacturers would need to be carefully trained. A manufacturing licence that lacked proper knowledge transfer would be akin to having a list of ingredients without the recipe.

The WHO has recently proposed to set up knowledge and tech transfer sites for mRNA vaccine manufacturing, specifically to train people from low- and middle-income countries.

“So obviously, the WHO doesn’t see that it is so complicated that a local manufacturer, even in the low to middle-income countries, couldn’t be taught how to do it,” Toole says. “And that’s very encouraging, particularly for future pandemics.”

In the meantime, big vaccine developers don’t seem keen to release their licences, appealing on their right to make a financial return. But vast amounts of public money poured into research and advanced purchase agreements have largely covered vaccine development costs, says Legge.

“And it’s not going to affect their profits – which are in the billions of dollars, by the way – because currently they simply can’t produce enough vaccines for the world,” adds Toole.

Companies should voluntarily release their licences, he says. “The Serum Indian Institute is so nimble at its job that once they had all the details, they could produce the mRNA vaccine within three to six months.”

India is the largest vaccine manufacturer globally, providing around 70% of the world’s vaccines (of all types). But factories are owned by vaccine developers. Therefore, paradoxically, most of the vaccines produced in India are shipped elsewhere, notwithstanding the tragic lack of doses in the country and the resulting inefficient immunisation campaign.

Suppose India was allowed to develop its capacity to produce mRNA vaccines. In that case, it could then share that technology with companies in neighbouring countries that also can produce vaccines, such as Thailand, Bangladesh and Indonesia.

“Under the international law [there] would be nothing to stop them from sharing that,” Toole says.

To approve the TRIPS waiver, all 164 countries that are members of the WTO would need to agree unanimously. For several months, the proposal had little traction due to opposition from the US, European Union, Norway, Canada, Australia, the UK, Switzerland, Brazil and Japan.

But in a notable shift, US President Biden recently announced that the US will support the campaign, mounting pressure on other countries and reopening the discussion. The European Union and New Zealand have expressed their willingness to negotiate.

On 6 May, the Financial Review reported that Australian Trade Minister Dan Tehan said he’d discussed the issue during a visit to Geneva for talks with WTO director-general Ngozi Okonjo-Iweala. “We welcome this positive development and look forward to working with the U.S. and others to find solutions that boost the global rollout of COVID-19 vaccines,” Tehan said. But he did not commit to the waiver proposal.

Finding an agreement could take months, if not years. A TRIPS waiver will do nothing to counter the immediate shortage of vaccine doses in poorer countries, where the virus is currently running rampant, but the campaign seems to have triggered some momentum around the scale-up of vaccine manufacturing.

The Biden administration, which had previously invoked the Defense Production Act to ban the export of raw material necessary for vaccine production, has recently released a one-off supply of filters to Indian manufacturers. Biden has also committed to delivering 20 million doses of vaccines produced by Moderna, Pfizer and Johnson & Johnson. “[The campaign] is pushing the rest of the world to take action,” says Legge.

The TRIPS waiver is a discussion we need to have, Toole says. “It makes sense to increase the production of vaccines to enable the rest of the world to have access.” But in the short term, high-income countries must let COVAX access doses. “We need to stand back and let COVAX do its job,” he says.

So far, COVAX has distributed about 63 million doses in low and middle-income countries. Toole describes this as “a drop in the ocean” considering that the goal was to deliver 2 billion doses by the end of 2021.

“The waiver would open the doors to wider production,” says Legge. “But if we were taking an equitable and efficient public health approach, countries that have vaccinated 20–30% of their population should hold off while the rest of the world catches up.”