Diagnostics
Mutations in the spike protein make it more difficult for monoclonal antibodies to bind to it, and prevent it from binding itself to target cells and reproducing.
patients to monitor how they react. All of this takes time. In contrast, Stamataki points out, once trials have shown monoclonals to be effective, then we know that they can be used relatively safely with these groups. A new, more-resistant variant, however, “can throw a spanner in the works for all the trials that are ongoing, to make sure that these monoclonals are appropriate for very special interest groups and at correct doses for the new variants”, says Stamataki.
“We don’t know where the new variants are going to come from, and they could be very different from the viruses we were dealing with as a population before.” Dr Zania Stamataki
Monoclonal antibodies are not difficult to develop, says Stamataki. The problem, however, is that “you have to go through the regulatory authorities again, and until you get approval you have got patients now who could have accessed that treatment, but they’re not allowed to have it.” She notes that, while sotrovimab was shown to be effective against Omicron, it appears to be less effective against the new Omicron variant, BA.2: “We know that one approved monoclonal works but because there’s a risk now of a new variant, regulators such as the FDA can limit its use to certain geographic regions where there is low incidence of BA.2, so it is logistically causing a lot of problems.”
Stamataki is concerned that the ability of new mutations to evade monoclonal antibodies is a disincentive to pharmaceutical companies to keep on developing them. The process of running safety trials, followed by efficacy trials, and then mass producing a
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drug, is expensive and time consuming. The risk, she says, is that “by the time a pharmaceutical company mass produces a monoclonal, then it may become obsolete because of the new variant.” An added difficulty, she notes, is that the patients most in need of monoclonal antibodies – those who are immunocompromised – are an “inherently difficult” cohort on which to conduct a randomised controlled trial. In less pressured situations than a pandemic, scientists will usually test virus mutations in a lab in order to test the efficacy of a particular drug in each mutation. This offers a potential way forward for developing effective monoclonal antibody treatments for Covid-19 in the future.
A silver lining
Broadly speaking, the future prospects for tackling Covid-19 are positive. The vaccines have proved successful and can be adapted to provide immune protection against different variants. “The beauty of the vaccine is that it’s a polyclonal response,” says Stamataki. “You don’t rely on a single epitope. You can bear to have a few mutations because you have other antibodies that are not incapacitated.”
Scientists now hope, she says, that Covid-19 will turn into a “more predictable evolving virus”. So far, there is no sign of that, demonstrated in how the variant to take over after Delta was not an updated version of Delta, but one that “came from left field”. The “silver lining”, she adds, is that Covid-19 has a proofreading mechanism, which is unusual among RNA viruses. This means it mutates less frequently than the flu, for example. “So we can catch up with this one,” she says. Gallagher is also optimistic that we will ultimately get the better of the virus: “I think the future of treatment of Covid-19, going a year or two down the road is going to be that you get tested, you’re positive, and you’re prescribed an antiviral, the way we deal with the flu now.”
Practical Patient Care /
www.practical-patient-care.com
Design_Cells/
Shutterstock.com
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