If we ever make a covid-19 vaccine who should be first to get it?

2020-08-12

IT IS August 2021, and the moment the world has been waiting for has finally arrived. After many false dawns, a vaccine against covid-19 has passed all the tests and is ready to be rolled out.

It has been an arduous journey, but at last vaccine manufacturers around the world are cranking out thousands of doses a day. The end of the pandemic is on the horizon.

But this isn’t the end. It isn’t even the beginning of the end. There are more than 7.5 billion people in need of vaccination but perhaps only a billion doses available in the first six months of production.

Who gets one? Everyone agrees that front-line healthcare workers must be first in the queue. But who should be next? What is the best way to attain herd immunity? Will people accept the vaccine? And is it possible to stop rich countries from hoarding the supplies?

The answers to these questions depend largely on decisions being made now, in 2020, long before a successful vaccine has been developed. Of course, that day may never arrive. But let us assume that it does. What happens next?

No single approach

Even if a vaccine works, there is no one-size-fits-all vaccination regime. The two newest vaccines to be developed give a flavour of the problem facing epidemiologists. These are the Ebola vaccine Ervebo, approved in November 2019, and a dengue fever vaccine Dengvaxia, approved in 2015.

Consider Ervebo. Before covid-19 stalled its roll-out there was enough time to devise and test containment strategies. These show that the most effective approach is ring vaccination. That means tracking down confirmed cases and vaccinating all of their contacts and all of their contacts’ contacts, thus throwing a ring of immunity around the virus.

For Dengvaxia, however, the most effective strategy depends on local circumstances. When the virus is rampant, mass vaccination offers the most protection to the largest number of people. But where transmission rates are lower, it is better to selectively vaccinate adults who have already had the virus. This is because a second bout is more dangerous than the first one due to the way the immune system ratchets up. That also means that vaccinating infants, who are unlikely to have had the virus, can backfire because the vaccine acts like a first bout.

So what works for one disease might be less than optimal for another, because diseases and vaccines are all different. For covid-19, the absence of both a vaccine and full understanding of the disease means that designing a strategy is a very inexact science.

A team led by Emma McBryde at James Cook University in Australia has started modelling possible scenarios, but the results are still under wraps. One thing we can say, however, is that ring vaccination isn’t going to work. Ebola is transmitted by contact with bodily fluids, so spreads relatively slowly, whereas covid-19 is a respiratory disease that spreads very rapidly.

Regardless of the specifics, the overwhelming rationale for introducing any new vaccine is to reduce severe illness and mortality. That holds true for covid-19. But there are other considerations, says Nicholas Grassly, a vaccine epidemiologist at Imperial College London who sits on the Strategic Advisory Group of Experts covid-19 vaccine group for the World Health Organization (WHO) but spoke to New Scientist in a personal capacity. “Vaccination for covid-19 is not just about health, it is about the economy and protecting essential services, too,” he says. “That is a little bit different from how vaccines are traditionally looked at. So the question is, who should we vaccinate to maximise the health benefits, facilitate a return to productivity and protect health and education services?”

That decision would be more straightforward if vaccine stocks were unlimited. But they won’t be, at least not at first; the most ambitious scale-up plan so far is by a vaccine team in Oxford, UK, which says it could produce 2 billion doses within 12 months of approval. It is possible that two doses will be needed per person, so that would only be enough shots for fewer than 1 billion people, allowing for a 15 per cent wastage rate.

“It is quite unlikely that there is going to be enough vaccine for the entire world,” says Beate Kampmann, director of the Vaccine Centre at the London School of Hygiene & Tropical Medicine (LSHTM). That means tough choices await.

The hard work has already started. The WHO published a preliminary vaccine allocation plan in June. It prioritises healthcare workers, of which there are about 50 million worldwide. Next are the 600 million adults over the age of 65, and then the 1.1 billion adults over 30 with cardiovascular disease, cancer, diabetes, obesity or respiratory disease.

Individual countries are also formulating plans. In the UK, the Joint Committee on Vaccination and Immunisation held an extraordinary meeting on vaccine prioritisation on 18 June. It started from the premise that the priority is to “save lives and protect the NHS”, a familiar slogan to anyone who has been watching the UK response to the pandemic.

To that end, the committee decided that healthcare workers must be the highest priority, followed by care workers. Next in line should be people at increased risk of disease and death from covid-19, which means older people and those with pre-existing conditions. Everybody else will have to wait, although perhaps not as long as people in lower-income countries (see “Vaccine nationalism”).

Herd immunity

The US Centers for Disease Control and Prevention is also exploring the options. Its plan similarly puts 12 million “critical health care and other workers” at the head of the queue, followed by 110 million other health workers and high-risk individuals. The general population – 206 million people – go to the back.

It is notable that none of these plans mention herd immunity, which arises when there are enough immune people in the population to stop a virus from circulating. Despite its somewhat tarnished reputation after “natural” herd immunity was briefly and unscientifically touted as an exit strategy in some countries including the UK, vaccine-induced herd immunity is still our best bet for ending the pandemic and even eradicating the virus. “We are going to need global herd immunity,” says Gavin Yamey at the Duke University Global Health Institute in Durham, North Carolina.

In short supply

Even if an effective vaccine is developed, it will take years to produce the estimated 14 billion doses needed to protect the global population. Why so slow?

Making vaccines at scale is a laborious process, with quality control taking up a big share of the resources. The world’s largest vaccine manufacturer, the Serum Institute of India, produces about 1.5 billion doses of various vaccines a year, which shows the scale of the challenge.

“Trying to come up with an approach for 7 billion people is an enormous undertaking,” says Robin Shattock, who leads the vaccine team at Imperial College London. “Currently the biggest number of vaccines that are made a year is about half a billion doses of polio vaccine. Nobody has made a billion doses of any vaccine globally in any single year.”

There is a reason that vaccine-induced herd immunity hasn’t yet been incorporated into planning, says Grassly. It is often taken for granted that mass vaccination covering between 60 and 70 per cent of the population will lead to herd immunity to the coronavirus, but it may not.

Vaccines are designed to protect individuals from severe illness or death, not to induce herd immunity. They sometimes produce it by preventing infection and transmission, but that is a happy accident. The nasal flu vaccine, for example, halts transmission of the virus and can therefore create herd immunity. For this reason, it is principally given to children to prevent them from infecting vulnerable older relatives who are unlikely to respond strongly to a vaccine.

But as yet we don’t know whether a covid-19 vaccine will work this way. “If vaccines become available, it will be because they are protective against disease,” says Grassly. “They may, or may not, also be protective against infection or transmission, but we don’t know yet.”

“Vaccination for covid-19 is not just about health, it is about the economy and protecting vital services”

If a vaccine does promise herd immunity, it would probably be worth revising the vaccination priorities to take advantage, says Grassly. We know, for example, that some people who don’t develop symptoms can still be highly contagious. There are also “superspreaders” who infect many more people than average. The difficulty will lie in identifying who those people are, but it may pay to prioritise vaccination for teachers and those working on public transport or in supermarkets, he says.

There would also be an argument for vaccinating children rather than vulnerable adults. “Healthcare workers should be first, then the intuitive thing is to prioritise the elderly,” says Alberto Giubilini of the Uehiro Centre for Practical Ethics at the University of Oxford. “But, paradoxically, the best strategy might be to vaccinate children. Their immune system responds better to vaccines. To reach herd immunity you want to give the vaccine to the people for whom it works best.”

It is even possible that the vaccine might not work in older people, in which case the strategy would be to vaccinate the people around them.

Another factor that could scupper herd immunity is what researchers call vaccine hesitancy. According to Heidi Larson, director of the Vaccine Confidence Project at the LSHTM, covid-19 anti-vaccine posts on social media outnumber positive voices by about four to one.

In denial

There are signs that the anti-vaccination misinformation is cutting through. In the UK, for example, Larson’s team has been asking samples of more than 2000 people whether they would be willing to be vaccinated. In late March, 80 per cent of people said yes. By the end of May, that had fallen to 67 per cent.

In the US, a poll conducted in May found that 42 per cent of people would definitely get vaccinated against coronavirus, 27 per cent definitely wouldn’t and the rest were unsure.

A similar obstacle is the growing number of people who refuse to accept that covid-19 even exists, says Leesa Lin at the LSHTM. “Covid-19 denialism is likely to pose a threat to convincing people to take a vaccine. There is a significant association between perception of the disease risk and vaccine uptake,” says Lin.

All told, then, the outlook remains highly uncertain. A vaccine may not even be possible. If it is, there won’t be enough to go round, at least at first. Even when there is, it may not induce herd immunity. And even if it does, too few people may choose to take it. The beginning of the end? Not likely. “If this was a 100-metre race, we have only run the first few metres,” says Yamey.

newscientist.com, 12 August 2020
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