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Promising antibody drugs might not work against new variants, scientists say

UK News

Antibody cocktail drugs that offered ‘great hope’ in treating Covid-19 are ineffective against worrying new variants of the virus, research suggests. 

Lab tests found the experimental treatments, known as monoclonal antibodies, failed to neutralise strains which emerged in Kent, South Africa and Brazil.

The drugs are derived from cloning a single antibody, a virus-fighting protein, found in people who’ve recovered from Covid. Scientists make thousands of copies of the antibody in a lab before injecting them into people who struggle to mount a natural immune response.   

One of the most promising monoclonal antibody candidates, made by Regeneron in the US, was used on Donald Trump on October 2 last year during his Covid battle and may have helped him recover.

Another, developed by British pharmaceutical giant GlaxoSmithKline, is currently being trialled in NHS hospitals as part of a massive Government-backed study into new Covid treatments.

Data around the drugs’ effectiveness on the new variants is limited, there are only two pre-prints in South Africa and China, but both strongly indicate they will not be successful.

The three new variants all have key mutations on their spike protein which change the way they look to the immune system and allow them to slip past some antibodies.   

It’s thought that because monoclonal antibody treatments are based on one single type of antibody that was effective against the original strain of Covid, they are unable to recognise the new strains. 

Whereas during Covid infection in a healthy person, several different types of antibodies and T cells are sent to clear the infection as part of a larger immune response. It means even if some of the antibodies can’t recognise the new strains, others will. 

Promising antibody drugs that are being trialled in the UK and were used on Donald Trump during his Covid battle might not work against new variants, scientists say

Promising antibody drugs that are being trialled in the UK and were used on Donald Trump during his Covid battle might not work against new variants, scientists say 

All three therapy contenders from Brentford-based GlaxoSmithKline (GSK), American biotech firm Regeneron and Eli Lilly fail in the face of one or more of the variants

All three therapy contenders from Brentford-based GlaxoSmithKline (GSK), American biotech firm Regeneron and Eli Lilly fail in the face of one or more of the variants

The specifically-engineered antibodies can work in a vaccine-like way, protecting a patient from severe disease, or can help to stimulate the patient's immune system to attack antigens. Pictured: Regeneron, New York

The specifically-engineered antibodies can work in a vaccine-like way, protecting a patient from severe disease, or can help to stimulate the patient’s immune system to attack antigens. Pictured: Regeneron, New York 

Researchers are now tasked with finding 'conservative' regions of the virus that do not mutate so they can be targeted with antibodies. Pictured: Eli Lill, California

Researchers are now tasked with finding ‘conservative’ regions of the virus that do not mutate so they can be targeted with antibodies. Pictured: Eli Lill, California 

Dr Nick Cammack, who heads up the Covid-19 therapeutics accelerator at the Wellcome Trust in London, told The Guardian: ‘The challenge came at Christmas when these new variants appeared – the South Africa and Brazil ones particularly. 

‘The changes the virus makes in its spike proteins actually throw off these antibodies.’ 

The treatment by GSK is still effective against the South African and Brazil variants, according to Dr Cammack, but is not against the UK strain that emerged in Kent.

WHAT IS MONOCLONAL ANTIBODY THERAPY?

Monoclonal antibody therapy is a form of immunotherapy that uses monoclonal antibodies (mAb). 

It’s given as an injection under the skin or through a drip into a vein. 

The treatment works in many different ways. It can work in a vaccine-like way, protecting a patient from severe disease, or can help to stimulate the patient’s immune system to attack antigens. 

Hybridoma technology is one method for producing large numbers of monoclonal antibodies – identical antibodies that are clones of a unique parent cell.

The process starts by injecting an animal, such as a mouse, with an antigen that provokes an immune response.  

B cells produces antibodies that bind to the antigen. These antibody producing B-cells are then harvested and used to culture more antibodies. 

The monoclonal antibodies are screened against their ability to work, with initial experiments in animals. 

Major technological advances have made the discovery and development of mAb therapies quicker and more efficient, deriving the antibodies from humans and not animals. 

Scientists can create a mAb that is specific to almost any antigen, and are working on one for the coronavirus.

The spike protein on the SARS-CoV-2 virus is the primary target being explored for potential Covid-19 monoclonal antibodies.

The aim is that by targeting the spike protein, the antibody will be able to neutralise the SARS-CoV-2 virus, therefore stopping it from infecting healthy cells. 

A particularly interesting avenue is giving them to people who aren’t infected yet as a preventative tool. If the antibodies are potent and long-lasting enough, they could provide sufficient protection for a period of time before a vaccine is found.

Research and development is underway to create antibodies for diseases such as rheumatoid arthritis, multiple sclerosis, Alzheimer’s disease, and different types of cancers.

But many are already in use both in the US and UK. 

Since 2008, 48 new mAbs have been approved, contributing to a total global market of 61 mAbs in clinical use at the end of 2017, according to the US FDA.  

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That is a huge blow for Britain because the Kent variant is already the dominant strain in the UK so any new treatment will need to target it to drive down transmission.

The N501Y on the Kent variant makes it at least 50 per cent more infectious than regular Covid and early data in the UK suggests it is also 30 per cent more deadly. 

Dr Cammack added: ‘So here we are with a virus that makes a change that actually helps it stick to the cell even better. So these monoclonals are lost.’ 

The South African and Brazilian variants, have a mutation called E484K, which is also on the spike protein that many antibodies would normally target. 

This mutation has already been proven to hamper the current wave of vaccines, but not enough to make prevent people from getting protection. 

In another worrying development this week, the E484K mutation was found in 11 cases of the Kent variant, suggesting that strain is evolving again.  

Researchers are now tasked with finding new regions of the virus other than the spike that do not mutate so they can be targeted with antibodies. 

Dr Cammack explained that mass sequencing and genetic sequencing of the virus from around the globe is needed to determine what the changes are and where the ‘conservative’ regions can be found.  

The monoclonal antibodies are still effective against the original virus and have been used in Europe and the United States – but because the new strains have an ‘evolutionary edge’ over that strain, scientists anticipate it was peter out in the coming months.

An early trial on 20 patients in the US suggested the new GSK antibody treatment, known as Vir-7831, was safe and did not cause any adverse health effects on the old variant. 

Monoclonal antibodies were thrust into he spotlight after it was announced that former US President Donald Trump was given an experimental cocktail of the proteins made by Regeneron following his Covid-19 diagnosis.

Although it wasn’t approved, the company agreed to supply a single dose for Mr Trump at the request of his physician under ‘compassionate use’ provisions.

Monoclonal antibodies are already being used to treat tetanus, Ebola and diphtheria and are described as ‘one of the most powerful tools in modern medicine’, according to a recent Wellcome report. 

However the treatment, which is being trialled against HIV, is expensive and can be difficult to make so wealthy countries have only seen the benefits of them. 

It comes as another 33 cases of the troublesome South African Covid variant have been spotted in Britain, health chiefs revealed yesterday amid growing fears over mutant strains that experts say could make vaccines less effective.

Public Health England claimed 143 people have now been struck down with the variant since it was first discovered on British soil in December – including five in Scotland and nine in Wales. None have been found in Northern Ireland.

Officials also announced they have found 11 cases of the Kent coronavirus variant which carries an extra mutation in Bristol. 

DailyMail Online


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