Tens of thousands of volunteers around the world are being injected with experimental Covid-19 vaccines as developers race to find effective prevention. A successful vaccine could be the escape hatch from a pandemic that in the space of half a year has cost hundreds of thousands of lives and trillions of dollars.

But the real test may depend on how many people have access to a vaccine. A majority of the world’s 7.8 billion people would likely need to be inoculated to reach the critical mass or “herd immunity” to significantly slow or stop transmission, experts say.

Finding a successful vaccine, or several, is not guaranteed, though researchers are hopeful from early trial results. But it could take months or years to deliver billions of doses to all corners of the world. That is even as production capacities are being built before the vaccines are approved.

Hurdles include vaccine approval in individual countries, gearing up manufacturing sites, delivery logistics and organising vaccination campaigns.

Public health experts say the more people that get the vaccine could be the difference between bringing the pandemic under control and a virus ping-ponging around the world to spark repeated outbreaks.

“The worst case scenario is vaccine nationalism, where countries take a me first or me only attitude,” said Jon Andrus, former deputy director of the Pan American Health Organisation, the World Health Organisation’s regional office for the Americas.

“The doses won’t be available all at once, they will come out in tranches, so [it’s about] being prepared with policy that will target groups most efficiently everywhere,” said Andrus, now an adjunct professor of global health at George Washington University’s Milken Institute School of Public Health in the US.

That could mean making a vaccine available first to vulnerable populations like the elderly, those with other illnesses, and frontline health workers, said Andrus, who helped steer the Americas through the acquisition of vaccines during the last pandemic, H1N1 influenza, in 2009.

It is a supply and demand challenge as countries jockey to secure supply for their own populations, with hundreds of millions of potential early doses already earmarked for Americans, Europeans, Indians and Chinese.

However, a coalition of health organisations has proposed a new model, known as the COVAX facility, to offer broader vaccine access.

The group formed by the World Health Organisation, the Global Alliance for Vaccines and Immunisation (GAVI), and the Coalition for Epidemic Preparedness Innovations (CEPI) aims to distribute 2 billion doses equally, based on population, between participating countries by the end of next year.

The plan itself is a break with past mechanisms that typically tried to reduce the time lag between rich nations and developing countries for first doses, according to Yvette Madrid, a Switzerland-based global health consultant who has advised the WHO on immunisation campaigns.

“It’s much more ambitious, and that makes the whole thing very difficult,” she said.

Some 165 countries, home to 60 per cent of the global population, could be covered by the mechanism, the WHO said earlier this month. But it is unclear whether the scheme will get the commitment it needs from rich and middle income countries and manufacturers.

“They need to reduce vaccine nationalism in order to have a chance to get access to the [global] supply,” Madrid said.

Countries are already acting to get a lock on potential vaccines. The United States has pledged billions of dollars in financing to secure candidates from pharmaceutical makers via its Operation Warp Speed platform, including 300 million doses from AstraZeneca and an initial 100 million from Pfizer. It is unclear how many doses people would need for initial immunisation.

France, Germany, Italy and the Netherlands also formed a “vaccine alliance” and reached an agreement with AstraZeneca to provide Europe with 300 million to 400 million doses from the end of the year. Pfizer is also in talks to supply vaccines to Europe, Reuters reported this week, citing the company’s chief executive.

“The AstraZeneca candidate, now in final phase 3 trials and developed in partnership with Oxford University, is also part of the WHO, GAVI, CEPI plan. The company may provide the coalition with 300 million doses starting at the end of this year.”

AstraZeneca has also given a licence to the Serum Institute of India to manufacture another 1 billion doses for lower and middle income countries. Half of those will go to India, company CEO Adar Poonawalla told television broadcaster India Today last week.

Other bilateral arrangements are in the works. China plans to provide a US$1 billion loan to make its coronavirus vaccines accessible for countries across Latin America and the Caribbean, the Mexican foreign ministry said last week
Philippine President Rodrigo Duterte on Monday said he had made a plea to Chinese President Xi Jinping to help his country get priority access to a Covid-19 vaccine.

Among the five final phase vaccine trials announced, two are using candidates developed by teams in China. A product developed by Sinovac Biotech is undergoing trials in Brazil and is expected to be made available to the population there.

Another Chinese candidate, developed by Clover Biopharmaceuticals but not among those to have reached phase three trials, is being funded as part of CEPI’s portfolio.

Xi has called vaccines produced in China a “global public good”. Last month, he said “once the development and deployment of a Covid-19 vaccine is completed in China, African countries will be among the first to benefit”.

Vaccine immunology works on the principle that if enough people in a population are inoculated, the chances of infection diminish. But much is unknown about whether and how Covid-19 vaccines will work. Some could prevent severe disease, but not stop transmission, virologists say.

Another risk factor could lie in how long immunity lasts and whether booster shots are needed, according to virologist Jeremy Rossman at the University of Kent in England.

“[Even] with a full countrywide vaccination campaign, the country could be at significant risk of another outbreak due to spread of the virus from other countries that have not been able to fully vaccinate,” he said.

Thomas Bollyky, director of the global health programme at the Council on Foreign Relations think tank in New York, said inequitable allocation could mean the virus was under control in some areas, “while it continues to rage, unabated in low income countries”.

He said he advocated a vaccine trade and investment agreement to boost access and ensure countries did not halt exports of doses or components to ensure their own supply.

In answer to a question about what would happen if a manufacturing country tried to prevent doses from leaving its borders, CEPI chief executive Richard Hatchett told US health publication STAT in April that that was why they were looking to manufacture the vaccine around the world.

But those agreements are not happening quickly enough, according to Sai Prasad, president of the Developing Countries Vaccine Manufacturers Network, a consortium of 40 manufacturers from 14 countries and territories.

“The innovation and the R&D is a very, very important part of the story, but that’s just to get the ball rolling,” he said.

Prasad also heads quality control at Bharat Biotech International, a Hyderabad-based company involved in developing India’s first Covid-19 vaccine candidate to go to human trials and is part of a GAVI advisory committee.

Next steps included ramping up manufacturing and getting international regulatory approvals, and all were critical for making global distribution a reality, but may not be processes small developers had experience with, he said. He said there were fewer than 100 vaccine makers worldwide and many specialised in a single type.

“It’s a highly technologically challenging field. So unless there is really a matchmaking that happens between these innovating companies and the large manufacturers [or multinationals] at an early stage, there will be a lot of delays in the future,” he said.

John Lim, executive director at the Centre of Regulatory Excellence of Duke-NUS Medical School in Singapore said medical regulators around the world faced unprecedented challenges.

They might have to review multiple new vaccine candidates, some of which were using technology that had never been approved before, he said.

“The challenge will be how to assess sufficient safety, quality, efficacy to give even conditional approvals for use of those vaccines in the first instance.”

However, Lim said he was encouraged by the level of access to information and international collaboration that was happening between regulators. “It’s fortuitous that a lot of these pieces have come into place already,” he said.

Even as manufacturers gear up and regulators do their own work, governments need to be thinking about the logistics, according to Charles Wiysonge, director of Cochrane South Africa, a non-profit health organisation.

The practical details included finding vaccine storage space, keeping supplies cold enough, allocating health care workers, and building trust among communities, said Wiysonge, who is part of the WHO African Regional Committee on Health Research and Development and part of GAVI’s independent review committee.

Many countries had experience with mass vaccination campaigns, he said, pointing to polio vaccinations in West Africa and measles immunisations in India.

“But those are nothing close to what we might be imagining now … potentially everybody needs this, from a newborn child to the oldest person in that country, it’s more complex,” he said.

Wiysonge said he felt hopeful about current initiatives, but other details needed to be carefully planned now.
“It’s one thing having the vaccines well stocked, but it needs to be delivered in a safe way.”