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Scientists are questioning whether waning immunity to Covid-19 could affect how useful a vaccine will be in tackling the pandemic, even as investors welcomed new positive early trial data.
A study from King’s College London, which has yet to be peer-reviewed, showed recovered patients’ antibodies declined significantly within months of infection, raising the critical issue of how long a vaccine could prevent people catching the disease.
The concerns come as shares in Moderna rose 6 per cent on Wednesday after the US biotech company shared positive data from its phase one trial showing all 45 participants had produced antibodies after taking its vaccine candidate.
Herb Sewell, emeritus professor in immunology at the University of Nottingham and a consultant immunologist, said the King’s College study appeared to show that antibodies to the virus disappeared more quickly than other coronaviruses, such as the Middle East Respiratory Syndrome, which had an immune response that lasted at least a couple of years.
“If the vaccine response drops off like the natural response does, it does mean we’d have to give repeat ones,” he said.
It is normal to see some decline in antibody loads after a vaccine, which will still be effective if the body can subsequently produce antibodies more quickly when exposed to the virus again. Importantly, the body does not always respond in the same way to a vaccine, as it does to an infection.
Tal Zaks, chief medical officer at Moderna, said he believed it was “entirely plausible” that the antibodies fade, but that it might be because those patients were asymptomatic or started with lower levels of antibodies.
“They seem to lose them more quickly, which probably speaks to the quality and type of immune response to begin with,” he said. “It's reassuring to see that we achieve neutralising antibodies that are consistently above what you see from people who've actually been sick, so we expect they are going to be protected.”
Betty Diamond, director at the Feinstein Institutes for Medical Research in New York, said the Moderna results were “encouraging” but more information was needed about how long the response will last. Participants’ antibody levels started to decline 41 days after the vaccine, but the trial data only went until 57 days.
“Vaccines present antigen differently than natural infection and use different adjuvants [chemical boosters], therefore there is no reason to assume the immune memory will be the same with vaccines as with natural infection,” she said.
It will be important that a vaccine induces a high level of antibodies from the start. Umer Raffat, an analyst at Evercore ISI, said on a call with investors that the participants’ response to Moderna’s potential vaccine has been “materially higher” than other candidates including those from US-based Inovio and Chinese company Cansino Biologics.
While it was hard to compare them directly, the Moderna vaccine also seemed to induce a better response than the vaccine being developed by Pfizer with Biotech, Mr Raffat said.
Both are using a novel technique called messengerRNA to transcribe the virus’ spike protein into a human cell to show it to the immune system.
Scientists and investors will be closely watching the longer phase three trials that Moderna and other vaccine makers are preparing to embark on this month, to see where the number of antibodies plateaux.
They are also interested in seeing how participants’ antibodies react when they come into contact with Covid-19 beyond the laboratory. Penny Heaton, chief executive of the Bill and Melinda Gates Research Institute, wrote in the New England Journal of Medicine that the laboratory techniques for confirming that there were antibodies in a participant’s blood were “notoriously variable”.
“Confirmation of the correlation between antibody titers [concentration] and protection against Covid-19 will be possible only in a large clinical efficacy study,” she wrote in an opinion article that accompanied the publication of the peer-reviewed data on Moderna’s vaccine candidate.
Given the concerns about possible declining levels of antibodies, experts are likely to examine more closely the response a vaccine induces from T-cells, another key part of the immune system.
Mr Raffat said he had heard AstraZeneca would show a robust response from both T-cells and antibodies to the vaccine it is developing with the University of Oxford,. AstraZeneca did not respond to a request for comment.
On the call with investors on Wednesday, Mr Raffat concluded: “If I want to take a vaccine in January, I’ll probably want to take Astra for a T-cell response and Moderna or Pfizer BioNTech for a neutralising antibody response.”