Prevention is the way to go and vaccines are the example, but we must not forget the treatments that remain in continuous development. What’s new on the monoclonal antibodies front?

In the Spring of 2020, the hyperimmune plasma caused a sensation, and several studies began all over the world, to understand its efficacy and establish how to use it. If you recall, hyperimmune plasma is derived from the blood of individuals who’ve been affected by SARS-CoV-2 and have recovered, so they have a high level of antibodies against the new coronavirus.

However, the use of hyperimmune plasma was (and remains) an emergency therapy because not all people affected by the infection are eligible and possess high-enough levels of antibodies against SARS-CoV-2 to be used (more on this here). In addition, the plasma collected must be treated before being infused in a patient with COVID-19, and finally it’s necessary that the blood group of the donor and recipient are compatible, and the entire procedure must be performed in hospital with significant associated costs. In summary, it’s a therapy suitable in case of emergency but not feasible on a large-scale and in a routine way.

From hyperimmune plasma to monoclonal antibodies

The next step in hyperimmune plasma therapy was the identification of monoclonal antibodies. Let’s see what they are….

When a virus attacks your body, your immune system develops an antibody response, and this response manifests itself in your body in a different way, depending on where the virus affects you and generates polyclonal antibodies, so different from each other. Within this immune response, there are antibodies more powerful in blocking the reproduction of the virus. The goal of researchers is to identify the best antibody, reproduce it in the laboratory in large quantities, and thus generate a very effective monoclonal antibody.

Are monoclonal antibodies also effective against variants?

As is well known, RNA viruses frequently mutate to adapt to a changing (and in most cases) hostile environment. Therefore, it’s not certain that a monoclonal antibody effective against a known strain of SARS-CoV-2 that’s currently present in the population will be equally effective against a new strain of the coronavirus.

Several global studies have started, based on this consideration. Among these, a European study that takes the name ATAC (Antibody Therapy Against Coronavirus) and is funded by the European Research Council. This study includes the Policlinico di Pavia, the Karolinska Insitute of Stockholm, the Institute for Research in Biomedicine of Bellinzona, the University of Braunschweig, and the Joint Research Center of the European Commission. The study was recently published in the prestigious scientific journal Nature.

What’s new about the ATAC study?

One of the greatest difficulties associated with finding an effective treatment using monoclonal antibodies lies in the fact that SARS-CoV-2 is constantly mutating, and the variants that spread can be more infectious and even escape antibodies.

The ATAC study led to the development of a bispecific antibody; that is, a monoclonal antibody capable of simultaneously recognizing two different SARS-CoV-2 antigens, and thus preventing the virus from binding to ACE2, which is the gateway for the coronavirus to enter human cells.

The researchers combined two natural antibodies into a single artificial molecule, and preclinical testing in mice demonstrated that this bispecific antibody also protects against the currently most prevalent and dangerous variants: the UK, South African, and Brazilian ones.

The development of the bispecific antibody was first simulated, modeled, and then synthesized in the laboratory; then administered to laboratory animals as per pre-clinical protocol.

The next step will be to undertake the path of clinical trials, to reach the commercialization of a marketable drug.

This post is also available in: Italiano


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