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In its efforts to produce vaccines and treatments, the research community has focused on neutralize antibodies, which prevent him fromto virus spike protein binds to the surface protein of our cells. Now, a study from the University of Lund (Sweden) reveals that non-neutralizing antibodies also confer protection once morest Covid.
“Non-neutralizing antibodies might also provide protection. This would mean that we have broader protection once morest antibodies than previously thought, which makes us less vulnerable to virus mutations», says Pontus Nordenfelt, who led the study and is a researcher at the
Lund University.
This large project has carried out a more detailed study on how the immune system also fights the virus through phagocytosis, the ability to ingest foreign particles, in patients with Covid-19.
Phagocytosis is a type of clearance mechanism during which components of the immune system target and ingest potential threats, such as bacteria or viruses, and this mechanism is facilitated if the harmful substance is marked by an antibody.
The results, published in a thematic edition of «
Frontiers in Immunology», indicate that the antibodies non-neutralizing They are also important in the fight once morest Covid-19, through this mechanism.
“We observed that many of the antibodies that develop in response to Covid-19 they are opsonizing, that is, they send a signal to the phagocytes of the immune system so that they ingest the virus. Our results indicate that non-neutralizing antibodies, as long as they can opsonize, can also provide an effective response to the virus”, adds Pontus Nordenfelt.
The findings are supported by experiments in mice, in which non-neutralizing antibodies protected the animals from Covid-19 infection.
The team also found that the amount of neutralizing antibodies affects the process of phagocytosis.
In addition, the study team identified and isolated immune system cells from the blood of recovered Covid-19 patients. Using various techniques, the researchers mapped which immune cells interact with the virus’ spike protein and identified the antibody binding sites. Subsequently, using flow cytometry, they studied how these antibodies affect phagocytosis.
The scientists coated micrometer-sized beads with the spike protein and, in doing so, observed that the dose of neutralizing antibodies had an effect on phagocytosis.
Opsonization is the immune system mechanism in which an increase in bound antibodies triggers a stronger phagocytic response. Surprisingly, maximal opsonization is already achieved with relatively low levels of antibodies.
Beyond this, the researchers noted a reduction in effect. Antibody binding itself continued to increase linearly, even as phagocytosis decreased, showing that it is the spike protein doing something that causes this reduced phagocytosis.
To make sure this wasn’t due to other factors, the researchers performed the same experiment, but this time using only monoclonal antibodies. This meant that only one type of antibody (clone) was used instead of the standard combination of thousands of different antibodies.
“It showed the same trend. Up to a certain level, there is a linear dose effect of the antibodies. After that, go down. Basically, when you give too high a dose, you don’t get the protective effect,” he says. Wael Bahnan, researcher in medicine of infections in the
University of Lund and first author of the study.
“It appears that something is happening to the spike protein that results in reduced interaction.”