LESS than a year after a new kind of coronavirus started spreading around the globe, we have several vaccines that seem to be very effective at producing strong enough immune responses to protect people from developing covid-19.
Despite this great news, however, critical questions remain about how our immune system responds to the virus. Speaking at an , Devi Sridhar at the University of Edinburgh, UK, listed some of the gaping holes in our knowledge. “How long does immunity last? Can you get reinfected? Is a vaccine going to provide immunity, for how long?” Immunity remains the pandemic’s “million dollar question”, she said.
Actually, make that $12 trillion, which is the amount governments have collectively spent propping up their ailing economies, according to Gita Gopinath at the International Monetary Fund. That financial haemorrhage will only stop once we have high levels of immunity in the population. “Either vaccine-induced immunity or some level of natural immunity is the only way out,” says John-Arne Røttingen, co-founder of the Coalition for Epidemic Preparedness Innovations (CEPI).
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Mixed early results
Throughout the pandemic, immunologists have been working hard to answer these questions. But the results have been mixed. On the key question of the duration of the immune response following infection, for example, some early studies concluded that it looked set to , but others that it would be
The vaccine trial results have enlightened us somewhat. According to a scientist who has worked on teams developing vaccines at drug companies, who spoke to New Scientist on condition of anonymity, vaccine developers usually aren’t that interested in the fine details of the immune response. Clinical trials are typically designed with one thing in mind – to apply for approval, and for that they only need to show that the vaccine is safe and protects against disease for the trial’s duration. The World 91ɫƬ Organization (WHO) and the US Food and Drug Administration have said they would like to see a minimum of six months’ protection.
“90%
The expected drop in immune response six to eight weeks after an infection”
With covid-19 vaccines, however, the drug companies have been gathering and releasing relevant data. A spokesperson for AstraZeneca told New Scientist that the vaccine it is developing with the University of Oxford induces a strong response in all the important elements of the immune system: antibodies, B-cells and T-cells, and memory cells. Pfizer and BioNTech have said that their vaccine activates antibodies, B-cells and T-cells. Moderna published data showing 90 days after receiving the second shot of its vaccine, but didn’t say anything about T-cells.
Academic research on natural immunity is also progressing and results are encouraging. “It’s not completely nailed down yet,” says Paul Klenerman at the University of Oxford. “But there’s emerging data from different groups, which is always good, that you can keep detecting measures of immunity over at least six months.”
He points to one of 185 people who had covid-19, including 41 who had it more than six months ago. Every measure the team looked at, including antibodies and T-cells, pointed to robust and lasting immunity. “They have a measure of everything and it looks pretty solid,” says Klenerman.
Other teams are finding similar things, he says. A , for example, looked at 100 people who had mild or moderate covid-19 more than six months ago, and found they had a strong response in some memory cells, which are important for long-lasting immunity.
“6 months
How long the WHO and US Food and Drug Administration want covid-19 vaccine immunity to last”
Eleanor Riley at the University of Edinburgh agrees that the picture is looking increasingly rosy. “There are papers following people who had the virus back in March and April. The antibody levels have dropped a bit, but they’ve stabilised and the T-cell responses seem to be pretty persistent as well,” she says.
The reason for the contradictory results earlier in the pandemic is probably that insufficient time had elapsed, she says. It is quite normal for an immune response to spike early on, then fall away precipitously, only to plateau after six to eight weeks. It then decays very slowly over months or years.
“I’ve done a lot of work over the years following people’s immune responses over time, and we see this over and over again, a 90 per cent drop from the peak to the plateau. But the plateau is what matters. This is why we now say it’s long-lived,” says Riley. Exactly how long-lived isn’t yet known, but Riley’s hunch is at least a year.
There are still some open questions. One is whether someone who has only a very mild or asymptomatic case also develops long-lived immunity. “We don’t quite know yet how much immunity you need to protect you,” says Klenerman. According to Riley, our current model of immunology predicts that mild or asymptomatic cases should produce only short-lived, local immunity in the lining of the airways rather than a vigorous response in the bloodstream, known as a systemic immune response, which is considered the most protective kind. “It does look as though people [who] have had asymptomatic infection, some of them make a rather trivial immune response,” she says. “That’s what we expect, but we’re still a little bit uncertain.”
“5-10%
Proportion of people who don’t seem to get protection from the vaccines in clinical trials”
The immune response of the airway lining is a neglected area of study, says Michael Russell at the University of Buffalo in New York. This is the initial site of attack and must play a key role in fending off the infection, but has so far taken a “We think it is a serious omission to ignore it,” says Russell. Understanding it better might hasten the development of nasal spray vaccines that could be easier to store, transport and administer, he says.
“Every measure the researchers looked at pointed to robust and lasting immunity”
Low reinfection risk
It also isn’t totally obvious what is going on with reinfection, but both Riley and Klenerman say this doesn’t look like a serious problem, even though there have been some reported cases. “Exactly why that happens is not clear,” says Klenerman. “But, fortunately, it doesn’t seem to be a major clinical issue at this point.”
Another apparent non-issue is immune-enhanced disease, where an initial immune response from infection or vaccination paradoxically makes people more susceptible to severe illness during a second bout. “Nobody has seen it,” says Riley. “That doesn’t mean it won’t happen, but if it does, my guess is it’s going to be very uncommon.”
All of which adds to the growing optimism over the ability of vaccines to end the pandemic. “It has followed the textbook, basically, and generated the kind of immune response you’d expect,” says Klenerman, though he warns that the trial results don’t tell us everything. In trials, vaccines didn’t work in around 5 to 10 per cent of people. “There’s a certain fraction of people that didn’t appear to get good protection in those trials. And we don’t understand why,” he says.
Another remaining unknown is whether any of the vaccines produce sterilising immunity, meaning they stop the virus from invading cells rather than just helping the body fight it off. This is important for herd immunity as sterilising immunity halts transmission and so can grind the disease to a total halt.
But according to Sarah Gilbert of the Oxford team, sterilising immunity isn’t necessary to slow the pandemic. A vaccine that somewhat reduces transmission – as the Oxford/AstraZeneca one appears to do – can slow the spread significantly, she says.
Riley is even more upbeat, especially about the duration of immunity. “I think the worst-case scenario is that people might need an annual booster, which they’ll almost certainly get as a combined flu-coronavirus vaccine.”
“Exactly why reinfection happens isn’t clear. But, fortunately, it doesn’t seem to be a major clinical issue”
She says she was always confident that a vaccine would be possible and nothing she has seen in recent weeks has changed her mind. “This always looked like a pretty straightforward virus to vaccinate against.”
