Antibodies-performance, to combat the COVID-19

Des anticorps ultraperformants pour combattre la COVID-19

Researchers in the us and the netherlands come to isolate from the blood of people who recovered from the Covid-19 antibody extremely powerful, capable to neutralize very low concentrations of the virus responsible for the disease.

When our immune system is put in the presence of an infectious agent such as the coronavirus SARS-CoV-2, certain white blood cells (B lymphocytes) will activate and start the production of antibodies designed to neutralize the virus.

It is a response to a hyper-specialized : each clone of advanced B-cell will produce an antibody that is different, recognizing a region (epitope) specific region of the virus, and it is for this reason that these antibodies are called monoclonal. Of course, these monoclonal antibodies will not have all the same ability to neutralize certain regions of the virus are less important for its biological activity, so that an antibody which interacts with one of these regions will have little impact on the infection.

However, when an antibody specifically interacts with a domain of the virus, which is absolutely essential for its activity, the potential for neutralization by the antibody will be significantly greater and may allow the elimination of the virus and lead to a cure.

Critical area

The molecular analyses of the structure of the coronavirus have shown that the region of the virus the more important for its activity is at the level of the peaks external, in particular the area known as the RBD (receptor binding domain) involved in binding with the membrane protein ACE2, and which is absolutely essential for the virus entry into the cells (1). Therefore, it is not by chance if the blood of convalescing patients, who have defeated the Covid-19 shows the presence of monoclonal antibodies directed against this region of the virus (2).

According to recent results, some of these antibodies have an affinity extraordinary for the portion of the RBD of the sars coronavirus and can therefore neutralize the virus at very low concentrations (3). From blood samples of patients who had been affected by the Covid-19 and had cured, the Dutch researchers were able to isolate 19 neutralizing antibodies directed against this portion RBD of the virus, 2 of which had neutralizing activity that is absolutely remarkable, with an interaction with the virus detected at concentrations as low as 7 nanograms (one millionth of a milligram or 0,000 000 001 g) per milliliter.

Anti-RBD as powerful (affinity of the order of ng/mL) have also been obtained by a group in california from the plasma convalescent from three different donors, and these antibodies have protected animal models (hamsters) exposed to very high amounts of SARS-CoV-2 (4). The detection of these antibodies, high-performance, in different individuals affected by the Covid-19 therefore suggests that the immune response to the coronavirus has similarities from one person to the other and that these antibodies contribute to the healing of this disease.

The union makes the force

Evolutionary pressure made it so that the virus must constantly adapt in order to improve their chance of survival, for example in mutant portions of their genetic material to become resistant to antiviral drugs. One of the potential problems of monoclonal antibodies against the coronavirus is a mere mutation of the virus in the region recognized by the antibody could completely abolish the neutralizing capacity of the antibodies and make it completely ineffective.

The researchers of the firm Regeneron have recently shown that you can alleviate this problem by using a mixture containing two antibodies directed against different regions of the coronavirus (5).

When the virus is exposed for a few generations of their reproductive cycle to the antibody, it actually succeeds to modify slightly the structure of his region, RBD and become completely resistant to each of the eight monoclonal antibodies developed by the researchers. However, when the virus faces a mixture of two antibodies that recognize each from a distinct region of the domain, RBD, he is unable to escape the pressure exerted by the antibody cocktail.

According to the authors, these cocktails of monoclonal antibodies may represent the future of antiviral therapy against the Covid-19 pending the development of a vaccine. Clinical trials with the antibody cocktail developed by Regeneron, which will start soon, should help answer this question.

(1) Lan J et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature 2020; 581 : 215-220.

(2) Ju B et al. Human neutralizing antibodies elicited by SARS-CoV-2 infection. Nature, published on may 26, 2020.

(3) Brouwer PJM et al. Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. Science, published on June 15, 2020.

(4) Rogers TF, et al. Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model. Science, published on June 15, 2020.

(5) Baum A et al. Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, published on June 15, 2020.

Share Button