Researchers look to blood antibodies as weapons in virus fight | Free to read
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Antibodies are emerging as weapons against coronavirus, not only in tests for past exposure to infection but also as potential treatments. They have already been given to thousands of patients worldwide in the form of blood plasma donated by people who have recovered from the illness.
Biotechnology and pharmaceuticals companies are working to create more sophisticated antibody medicines — some developed in animals — as confirmed virus cases worldwide pass 4.2m.
How do antibody treatments work?
Antibody drugs work in the same way as the body’s own immune system, by attacking the Sars-Cov-2 virus that causes Covid-19. They are biological molecules made in living cells, in contrast to well-publicised antiviral drugs such as remdesivir and hydroxychloroquine, which are synthetic chemicals.
In principle, this biological targeting should make antibodies more effective than the chemical drugs, with fewer side-effects. The primary target of the antibodies is the “spike protein” that Sars-Cov-2 uses to enter and infect human cells.
Babak Javid, an infectious diseases consultant at Cambridge University Hospitals in the UK, said antibody therapy could be seen as a type of “passive immunisation”.
“While a true vaccine educates your own immune system to recognise and attack a virus, with antibody therapy you’re getting the temporary benefit of an immune system from someone else — which might protect you for a month or six weeks.”
Antibodies that target the virus are distinct from another set of antibody drugs being tested to damp down the overactive immune system which causes severe symptoms in some Covid-19 patients. These immunomodulators were developed for other diseases such as rheumatoid arthritis and are not specific treatments for coronavirus.
How are these treatments being used?
Plasma — the fluid left behind when all the cells are filtered out of blood — has been used successfully for more than a century as an emergency treatment in epidemics, from the 1918 Spanish flu through to the 2014-16 Ebola outbreak in west Africa.
Survivors donate blood when they have recovered from illness and are no longer infectious, and the antibody-rich plasma is transfused into current patients to boost their immune systems.
More than 7,200 people in the US have received so-called “convalescent plasma” from patients who have recovered from Covid-19. Thousands more are expected to be treated over the next few weeks, said Arturo Casadevall, professor of molecular microbiology and immunology at Johns Hopkins University.
Biotech groups and university laboratories are also working on another method that involves extracting and purifying a mixture of antibodies from pooled donor plasma in the form of “hyperimmune globulin”.
Once researchers have identified the antibodies that target and neutralise Sars-Cov-2 most effectively, they can manufacture them in animal cells rather than extracting antibodies from donor blood plasma. This would allow them to greatly expand production.
“We will probably need to make a cocktail of two or three antibodies that neutralise the virus,” said Prof Javid. “If the antibodies work in slightly different ways, that will be potentially a more potent and effective treatment than if they all target and work through exactly the same mechanism.”
Who is working on these therapies?
At least 20 pharma and biotech companies in Europe, Asia and North America are committing substantial resources to antibody therapy.
GlaxoSmithKline of the UK teamed up with Vir Biotechnology of the US to develop an antibody originally identified from patients who recovered from Sars, the related coronavirus outbreak in the early 2000s. It also has a strongly neutralising effect on the new Sars-Cov-2 virus. Two forms of this antibody, code-named VIR-7831 and VIR-7832, are expected to begin clinical trials this summer.
AstraZeneca, another UK drug company, has more than 50 people working on antibody development. “We have narrowed thousands of candidates down to a top 10 and we should be nominating our two best antibodies by the end of this week,” said Mene Pangalos, the company’s head of biopharmaceuticals research and development. “We hope to be in the clinic in the July to September timeframe.”
AstraZeneca, like most of its competitors, plans to make its antibodies in genetically modified Chinese hamster ovary cells in vast bioreactors. These are the mammalian cells most commonly used for mass production of therapeutic proteins.
However, South Dakota-based SAB Biotherapeutics is producing mixed antibodies against Sars-Cov-2 in a herd of cows that has been genetically altered to produce a human response to viral infection.
Will it work?
Johns Hopkins University’s Prof Casadevall, one of the leaders of the US plasma programme, believes there is good reason to be optimistic about the treatment, based on his experience with other viruses.
“I think we are going to have an indication whether this is working very soon,” he said, predicting “a definitive answer in a couple of months”.
But he also made it clear that, since there were still so many questions about the way the human immune system responded to Sars-Cov-2, it was impossible to be sure.
Whatever the production system, “the biggest problem any antibody programme will face is to find enough manufacturing capacity”, said Dr Pangalos of AstraZeneca.
“It’s going to be a huge challenge to make millions of doses, and hundreds of millions of dollars will be at risk. We’ll have to partner with governments and others to make it work.”