19 – How does an antibody drug work and when is it useful?

The federal government has bought a new antibody-based Covid-19 drug for Germany. According to the Ministry of Health, these are preparations from the US companies Regeneron and Eli Lilly, which will initially be used in university hospitals. How do such means work and when are they useful? We answer the most important questions.

What are antibodies

Antibodies are proteins – that is, proteins – that arise as part of the body’s immune response. In other words, if you become infected with a pathogen – for example a virus – the body’s defense system becomes active and produces defense molecules that are directed against the characteristic structures of this pathogen: the antibodies. These are produced in large quantities in the course of the infection and are able to bind the pathogen, neutralize it and render it harmless. After the infection, the body “remembers” what the pathogen looks like so that it can react more quickly in the event of a second infection.
In the case of an infection with Sars-CoV-2, antibodies can be detected about two weeks after the infection, in the case of an illness, about one week after the onset of symptoms. According to new findings, published in the specialist journal Science, another type of antibody can be detected in the blood of those who have recovered for another six to eight months.
In addition to the formation of antibodies, there are other parts of the immune response that help fight the pathogen. Other cell types of the immune system are involved in this.

What are monoclonal antibodies?

“Monoclonal” means that the antibodies all arise from a cell clone, that is, they are the same. They are produced in the laboratory and are highly specific against a characteristic feature of the pathogen, such as part of the “spike” protein that Sars-CoV-2 uses to penetrate certain body cells. In contrast, recovered Covid-19 patients have a mixture of different antibodies against parts of the virus in their blood; one speaks of polyclonal antibodies. Each type of antibody is directed against a certain characteristic of the virus, so it can bind to different places.

How are antibodies used as a drug against Covid-19?

The principle is to give the body a head start: by giving antibodies, one skips the phase of the immune response in which the body is busy recognizing characteristic virus structures and producing suitable antibodies itself. In connection with the corona pandemic, two preparations from the USA are known, which received emergency approval there in November. They come from the Regeneron and Eli Lilly companies. The main difference: Eli Lilly’s drug contains a type of monoclonal antibody, while Regeneron’s drug contains a mixture of two monoclonal antibodies. The advantage of a mixture is that the additional points of attack increase the likelihood of effectiveness. Former US President Trump was treated, among other things, with the Regeneron preparation, which at that time was not yet approved in the USA either.

What are the side effects?

In general, therapies with antibodies are well researched because they are also used to treat other diseases such as cancer and rheumatism. In a clinical study, people treated with the Regeneron drug did not experience any increased number of severe side effects compared to the control group. According to the US Food and Drug Administration (FDA), Eli Lilly’s drug had serious side effects in two of 850 cases examined. The following applies to both preparations: There is a risk of hypersensitivity reactions. In addition, there is not enough data yet to make a definitive statement on this issue. Some side effects may not yet be known.

Antibodies and Virus Mutations

Preparations with a mixture of different monoclonal antibodies can help prevent mutations from taking hold. If the virus multiplies, such variants arise – most of them are of no advantage or even harmful to the pathogen and disappear again. In rare cases a mutation or a combination of different mutations can have advantages for the virus, for example because it can spread faster, as is the case with the virus variants first detected in Great Britain and South Africa. If the virus is only confronted with a single, very specific “weapon” such as a type of monoclonal antibody, mutants that this antibody does not recognize will prevail. One speaks of selection pressure. Mixing different antibodies will reduce the chance of this happening.

Why not use antibodies as the standard therapy against Covid-19?

There are mutliple reasons for this. On the one hand, there is currently no European approval for either the Regeneron or Eli-Lilly product, and according to the European Medicines Agency – EMA for short – a corresponding application process is not yet running either. Regeneron has announced that it will apply for European approval together with the pharmaceutical company Roche. In addition, antibody therapy does not always make sense. Because of its mode of action, such a treatment achieves the best results, especially at the beginning of an illness. Then it can prevent serious disease progression. From the study data available so far, it appears that those who received the preparation in the first ten days after infection benefited most from the treatment. Patients who already have severe Covid 19 symptoms – for example, who are in hospital and are receiving oxygen – are not allowed to receive such a drug. One possible explanation for this is that severe symptoms of a second phase of Covid-19 are caused by the reaction of the immune system. An active ingredient against the virus would simply come too late here. In addition, such a drug must be administered by infusion, which in this case takes about an hour and can only be done in clinics. In addition, the production of antibodies is complex and therefore expensive. The cost is estimated at around 2,400 euros per dose.
Another problem: Antibodies are foreign proteins – and what the body does not know it breaks down: The agent would therefore have a limited effectiveness and – unlike a vaccination, for example – does not protect against future infections.

Special case of convalescent plasma

Convalescent plasma is nothing else than blood plasma from convalescent patients. It contains – often depending on the severity of the illness – antibodies that the immune system has produced itself, i.e. a mixture of polyclonal antibodies. If it is available, it can be given to newly infected people to protect them from illness or a severe course of the disease. In this case one speaks of passive immunization. This type of therapy has already been used several times in epidemics, such as the 2014 Ebola outbreak in West Africa. The Paul Ehrlich Institute considers such a treatment to be a possible therapy option for Covid-19. However, the effectiveness of this has not yet been proven by studies.

(Stand 24.01.2021)

Further articles on the coronavirus

We have created a news blog. In view of the large amount of information, this provides an overview of the most important current developments.

+ Current developments: Figures on the coronavirus in Germany (as of February 18)
+ Interjection from the editorial staff: How to deal with numbers in the corona pandemic (as of February 17)
+ Extended lockdown: what rules apply and what opening perspectives are there? (As of February 17)
+ New rules: How the federal states implement the lockdown resolutions (status: 17.2.)
+ Border controls: what to watch out for (as of February 15)

Test and protection

+ Protection: The vaccination ordinance: who will be vaccinated first, who later? (As of: February 17th)
+ Dates: how, when and where can I get vaccinated? (Status: February 12th)
+ Vaccinations: What is known about the side effects of the corona vaccine (as of February 16)
+ Astrazeneca vaccine: reports of side effects and acceptance problems – experts disagree (17.02.)
+ Protection: So it is about the development of vaccines against the coronavirus (as of February 15)
+ Change of strategy: are rapid tests the breakthrough in fighting pandemics? (As of February 16)
+ Sick people: New insights into the search for drugs (as of January 30)
Treatment: How does an antibody drug work and when is it useful? (As of January 25th)
+ Economy: How the world of work deals with the number of infections (as of February 16)

Contagion and Transmission

+ Virus variants: how dangerous are the new mutations of the coronavirus? (As of: February 17th)
+ Opponents of infection protection measures: What AfD and lateral thinkers have to do with the spread of the coronavirus in Germany (as of 02/09)
+ Transfer: What role do aerosols play (as of January 22)
+ Excess mortality: How deadly is the coronavirus really? (Status: 05.02.)
+ Travel warning: The current list of risk areas (as of February 17th)

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