The extraordinary ability of SARS.CoV-2 to evade itself through successive mutations (changes in the genome, the genetic code of the virus) has been invalidating the defenses. Some drugs have been losing effectiveness at the rate that variants, lineages, sublineages or recombinations appeared. In December 2022, the emergency working group of the European Medicines Agency (EMA) stated: “In view of the mutations that have occurred in the coronavirus spike protein (...) it is unlikely that monoclonal antibodies currently authorized in Europe can maintain their effectiveness. All of them, without exception.” Several laboratories had managed to develop these therapies against the first variants of the coronavirus.
The body produces antibodies to defend itself, but immune system proteins can also be made in a laboratory from cells taken from people who have recovered from an illness. Antibodies directed at a specific protein (such as that of the SARS-CoV-2 virus) are called monoclonal. They attach to the virus and prevent it from penetrating and replicating in the body's cells to prevent and fight infection.
These are relevant drugs for people who do not respond to vaccines or are frail or immunocompromised. Therefore, the loss of its effectiveness remains a problem. Although the incidence and fatality of Covid have fallen drastically, in the last week recorded in Catalonia, 1,419 cases were diagnosed and 254 patients remain hospitalized, of which 7 are in the ICU.
Hence the relevance of the discovery by groups of researchers from the Hospital del Mar, IrsiCaixa, the National Center for Biotechnology (CSIC) and the Center for Genòmica Regulation: a monoclonal antibody active against all existing variants of SARS.CoV-2, including the currently circulating omicron subvariants (JN.1 and, to a lesser extent, BA.2.86).
This antibody, called 17T2, was isolated from the blood samples of an infected patient in March 2020, during the first wave of the pandemic. “The idea was that it could neutralize the ancestral virus, that of the first wave. Later we saw that it was also capable of neutralizing all variants, including the entire Omicron sublineage. We were testing whether it continued to respond and, very surprisingly, it continued to maintain this neutralizing activity,” explains Giuliana Magri, leader of the study, published in Nature Communications.
In his opinion, the key to the development was the strategy followed to obtain the antibody from a patient in the first wave. Using genetic engineering techniques, the researchers reproduced the antibodies in the laboratory and proceeded to evaluate in vitro their ability to bind to the virus and block it in the different variants. According to Benkamín Trinité, researcher at IrsiCaixa, “having an effective treatment even if new variants of SARS.CoV-2 appear can change the rules of the game when it comes to fighting the infection.” The special feature of 17T2 is that it can bind to a wide area of the virus spike (receptor).
The researchers have patented the new monoclonal antibody. “It has a lot of potential because it could potentially neutralize the variants that are going to come, which we don't know what they will be like,” says Dr. Magri with an enthusiastic tone in a telephone conversation. Although it has not yet been tested in patients. There are conversations with the pharmaceutical industry to find a company that will take on the challenge of developing the clinical phase and production of the antibody, extremely expensive processes.
In addition to the therapeutic capacity it has demonstrated in a mouse model, significantly reducing lung lesions and viral load, the antibody has shown prophylactic activity. It will not replace the vaccine, but it is a candidate for preventive interventions in immunosuppressed patients or those who respond ineffectively to vaccines.
