By Sarah Zhang
This could reduce the lag time between the approval and the availability of a vaccine, since companies might otherwise wait for FDA approval before scaling up manufacturing. But making hundreds of millions of doses is still a considerable challenge, especially for a novel vaccine.
The leading Covid-19 vaccine candidates rely on technology that has never been used before in approved vaccines. Moderna’s vaccine, for example, is a piece of RNA (ribonucleic acid) that encodes a coronavirus protein. Oxford and AstraZeneca’s vaccine attaches a coronavirus protein to a chimpanzee adenovirus. Neither has been manufactured before on the necessary scale.
Consider what happened in 2009, the most recent time the world mobilised to produce vaccines to stop a pandemic. The disease was H1N1, more commonly known as the “swine flu”, and vaccine makers had the much simpler task of subbing the H1N1 strain into the seasonal flu vaccine they make every year.
Despite many, many years of experience in making flu vaccines, the manufacturers hit an unexpected snag. Most flu vaccines are made from viruses grown in chicken eggs, and for some reason, the H1N1 strain did not grow very well in the eggs at first.
“The amounts produced from a given amount of eggs were much lower than normal. So that really delayed things,” says Goodman, who led the FDA’s pandemic response in 2009. But once millions of doses were in the works, Goodman says, there weren’t enough facilities that could package the bulk vaccine into individual vials.
The US Department of Health and Human Services created a network of fill-and-finish facilities to address this problem in the future. Right now, Operation Warp Speed is also awarding contracts for making the millions of syringes and glass vials needed to package a Covid-19 vaccine.
Demoralising scenario possible
Without careful planning on these fronts, the US could run into a demoralising scenario where vaccines are available but there is no way to physically get them to people.
Even if all of this goes well – the earliest candidates are effective, the trials conclude quickly, the technology works – another huge task lies ahead.
This is that when vaccines are approved, 300 million doses will not be available all at once, and a system is needed to distribute limited supplies to the public. This is exactly the sort of challenge that the US government has proved unprepared for in this pandemic.
In the case of the H1N1 pandemic, the US government purchased the vaccines and allocated doses to state and local health departments, which in turn vaccinated people through mass clinics as well as employers, schools, hospitals, pharmacies and doctor’s offices.
Nationwide, the programme eventually vaccinated about a quarter of all Americans – with demand falling because the pandemic itself peaked not long after the vaccine became available.
The 2009 vaccination programme was built on the infrastructure of the Vaccines for Children Programme, in which the CDC buys and distributes vaccines to states for children who usually are uninsured or on Medicaid.
Immunisation managers working in these programmes are well versed in the intricacies of vaccine storage and distribution, such as maintaining a cold chain for vaccines that could become ineffective at room temperature. But because they work with children’s vaccines, they deal mostly with paediatricians’ offices.
“We didn’t have relationships with hospitals and internists and people who vaccinated adults,” says Kelly Moore, who was the director of the Tennessee Immunisation Programme in 2009.
In August that year, two months before they got their first shipment of the vaccine, Moore’s team created a sign-up on the state immunisation registry and sent out a newsletter every Friday with updates and training modules for handling vaccines.
“Unfortunately,” says Moore, “that network has not been maintained because we haven’t had other vaccines to send them in 11 years”.
Contact information is out of date. Rebuilding this network for adults will be even more important with Covid-19. Although the H1N1 vaccine was recommended for all ages, the focus was on children, for whom the flu was particularly dangerous. The opposite is true of Covid-19, which is more of a threat to older adults.
Some of the leading Covid-19 vaccine candidates could also pose new logistical challenges, if they require storage at temperatures as low as -80 degrees Celsius or multiple doses to be effective.
In fact, a Covid-19 vaccine will quite likely require two doses; the first primes the immune system, allowing the second to induce a stronger immune response. Officials would have to balance giving one dose to as many people as possible and giving a second dose to those who already had one.
“That was a complication we didn’t face in 2009, and we were so grateful,” says Moore.
The CDC took the lead in distributing H1N1 vaccines in 2009 but Claire Hannan, the executive director of the Association of Immunisation Managers, says the agency has been oddly silent about plans for a Covid-19 vaccine since April.
“Initially, we were having planning calls with CDC right away. And then nothing,” she says, adding: “We continue to ask CDC these many, many questions. And they don’t know.”
She says she has unsuccessfully tried to get in touch with Operation Warp Speed, which has suggested that the Department of Defence may also get involved in vaccine distribution.
The CDC’s Advisory Committee on Immunisation Practices is also normally responsible for recommendations on how to prioritise vaccines. The committee, which is composed of outside experts, last met in late June and discussed prioritising vaccines for health-care workers, the elderly and those with underlying conditions.
The committee also considered prioritising vaccination by race, given the racial disparities in Covid-19 cases. But now the National Academy of Medicine is convening a panel on the same topic, which is again causing confusion about who is responsible for making these decisions.
In 2009, Moore’s job was to put the CDC advisory committee’s recommendations into practice. Two or three times a week, she would get an email from the CDC’s vaccine distributor letting her know the number of doses available for her entire state.
In practice, though, an initial shipment of vaccines might not be enough to cover everyone in even the highest priority group, such as healthcare workers.
It was up to people like Moore to decide which hospital got how many doses, with the promise of more on the way next week. Then individual hospitals administered the actual vaccines to their employees based on priority status.
This system is meant to be flexible and responsive to local conditions, but it also means that the availability of a vaccine might seem to vary from place to place.
For example, Emily Brunson, an anthropologist at Texas State University who studies vaccines, says that in 2009 there were cases in which one district interpreted recommendations strictly, giving the vaccine only to high-priority groups, while a neighbouring district offered it to anyone who wanted it.
The decision to distribute the vaccine through employee health centres in New York, which happened to include several Wall Street firms, also caused a big backlash.
“There are many ways that things can be misinterpreted,” Brunson says. And during an initial shortage, these decisions can feel unfair – especially given tensions seeded earlier in the pandemic when the rich and the famous were getting Covid-19 tests while ordinary people were being turned away at clinics.
If the pandemic so far is any indication, a vaccination programme is likely to take place against a backdrop of partisanship and misinformation.
Already, conspiracy theories are spreading about a Covid-19 vaccine, some of them downright outlandish. But the emphasis on speed – as in “Operation Warp Speed” – has also created real worries about vaccines being rushed to market.
At a recent congressional hearing with five vaccine makers, company officials had to repeatedly push back against the idea that the industry might cut corners for a Covid-19 vaccine.
“We’re going to be in a situation where some people will be desperate to get the vaccine and some people will be afraid to get the vaccine. And there’ll be probably a lot of people in between who are a little bit of both or not sure,” says Michael Stoto, a public-health researcher at Georgetown University.
A vaccine, especially a novel one that doesn’t offer complete protection against Covid-19, will require careful communication about risk.
“The fact that we can’t get ourselves straight about wearing masks will make that harder,” Stoto notes. Given the number of Americans who are currently unsure of – or opposed to – getting a Covid-19 vaccine, Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, has warned that even a vaccine might not get the country to herd immunity if too many people refuse it.
For the Americans pinning their hopes on a vaccine, a botched rollout could feel like yet another example of failure in the time of Covid-19. That could have disastrous consequences lasting well beyond the pandemic itself.
Brunson worries that such a scenario could undermine trust in public-health expertise and in all vaccines. “Both of those would be disasters,” she says, “in addition to the COVID itself being a disaster.”
She says it could mean, for example, further resurgences of vaccine-preventable diseases such as measles and an even bigger challenge when battling future pandemics.
For all the uncertainties that remain ahead for a Covid-19 vaccine, several experts were willing to make one prediction. “I think the question that is easy to answer is: ‘Is this virus going to go away?’ And the answer to that is, ‘No’,” says Karron, the vaccine expert at Johns Hopkins.
The coronavirus is already too widespread. A vaccine could still mitigate severe cases; it could make Covid-19 easier to live with. The virus is likely here to stay, but eventually, the pandemic will end.