SINCE THE beginning of 2020 medical researchers have been in hot pursuit of covid-19. One of their most important goals is to understand the immune response to SARS–CoV-2, the virus that causes it. Finding out what a good response looks like, and how long it lasts, is crucial. The answers will reveal whether people who have recovered from the illness are protected from a second infection, and also indicate how difficult it will be to develop a vaccine.
There is much to worry about. Over the past year, many reports have shown rapidly waning levels of covid-specific antibodies after the initial burst caused by an infection. Antibodies are parts of the immune system that attack the virus directly. They are expected to be involved in any long-term protection against reinfection. If they disappear quickly, that looks, on the face of things, like bad news. Worriers also highlight the facts that immunity to types of coronavirus which cause the symptoms described as “a cold” is short-lived, and that there are already a number of proven cases of reinfection with SARS–CoV-2.
Yet antibodies tell only part of the story. Another important actor is the T-cell (pictured above). Rather than attacking viruses directly, T-cells attack infected cells, to stop the virus reproducing. The balance of importance of the antibody and T-cell arms of the immune system varies with the illness in question. And, as far as this particular infection is concerned, although almost all patients who catch SARS–CoV-2 are thought to create T-cells in response, an understanding of their significance has been elusive.
This is largely because T-cells are harder to measure than antibodies, and so are less often studied. Shamez Ladhani, a consultant epidemiologist with Public Health England, a government health-protection agency, who has worked on a new, long-term investigation of these cells, says it took nearly three weeks to count them in the 100 patients his study looked at. The effort was worthwhile, though, because it has shed new light on how long-lasting this form of immunity to SARS–CoV-2 might be.
To a T?
Dr Ladhani’s project is part of a wider effort focused on health-care workers that Public Health England began in March. Over 2,000 people have donated blood samples every month since then. The 100 he and his colleagues have studied are a subset of these. In a paper just published as a preprint, but not yet peer reviewed, they say that six months after infection all of these patients, even those who had had only mild symptoms, or none at all, still had detectable levels of T-cells directed against the virus. Though their antibodies might have vanished, T-cells remained on the scene.
These findings bode well for the idea that T-cells offer long-term protection against reinfection, says Eleanor Riley, a professor of immunology at the University of Edinburgh. And Paul Moss, a haematologist at the University of Birmingham, says that his experience with other viruses leads him to expect the T-cell response Dr Ladhani has observed will last many more months than the six it has persisted for so far. In SARS–CoV-1, the name now given to the virus that caused the original SARS outbreak, in 2002-03, this form of cellular immunity was found to last in some people for over a decade. The long-lived nature of such T-cell responses fits in with the observation that, so far, reinfections seem rare.
Dr Moss says the implication of the new study is that those searching for vaccines against covid-19 should give priority to the production of T-cells. There is more good news here. Two of the leading candidates—one from a collaboration between Pfizer, an American drug company, and BioNTech, a German biotech firm, and the other from a second joint effort, between AstraZeneca, a British-Swedish drug company, and the Jenner Institute of Oxford University—do exactly this, while also stimulating the production of antibodies. Speaking in July, when the first results from the AstraZeneca-Oxford vaccine were published, Adrian Hill, the Jenner Institute’s boss, was keen to highlight the “excellent” T-cell response their vaccine created. “That is what this vaccine type does,” he explained. “That is what it is designed for.”
The significance of T-cells was obvious to Pfizer and BioNTech as well. In July they switched the focus of their efforts in response to data suggesting that an experimental vaccine they had hitherto regarded as secondary was eliciting strong T-cell responses. The coming weeks are likely to produce results concerning whether one or more of these putative vaccines actually provides protection against covid-19. That the two leading candidates provoke strong T-cell responses is grounds for optimism that vaccinology is on the right track.
As for the vanishing antibodies, there may be grounds for optimism here, too. The fact that levels of these proteins wane rapidly after infection, when they are no longer needed, should not be so surprising. It might not matter, either. The immune system could well be primed to make them in large numbers again, if and when it re-encounters SARS–CoV-2. It is also worth remembering that, even if researchers cannot detect antibodies, that does not mean they are not there at all.
As winter approaches in the northern hemisphere, the scientific fight against covid-19 feels more urgent than ever. But, while it is true that science has not yet jammed the pandemic exit doors open, there are now at least a few shafts of light emerging around the doorway. ■
This article appeared in the Science & technology section of the print edition under the headline “Teed up”