Non-neutralizing antibodies likely to protect against COVID, says study

When researchers talk about COVID-19 antibodies, they usually refer to neutralizing antibodies, which defend humans by preventing the virus from entering cells. Non-neutralizing antibodies may also be crucial in giving protection against COVID-19, according to a recent study from Lund University in Sweden.

Researchers identify non-neutralizing antibodies may prevent Covid
Pontus Nordenfelt and Wael Bahnan. Image Credit: Lund University.

Our results indicate that non-neutralizing antibodies could also provide protection. This would mean that we have broader protection from antibodies than previously thought, making us less vulnerable to mutations of the virus. It warrants further investigation.”

Pontus Nordenfelt, Researcher, Lund University

Pontus Nordenfelt led the research.

The scientific community has concentrated on neutralizing antibodies, which block the virus’s spike protein from sticking to the surface protein on human cells, to develop vaccines and therapies.

A more specific examination of how the immune system fights the virus in Covid-19 patients using phagocytosis, the capacity to absorb foreign particles, was carried out in a huge project carried out by researchers at Lund University.

Phagocytosis is a cleansing mechanism in which immune system’s players target and ingest possible risks like bacteria or viruses. This mechanism takes place when the hazardous particle is identified by an antibody. Non-neutralizing antibodies are also vital in the defense against Covid, according to the findings, which were published in a special edition of Frontiers in Immunology.

We observed that many of the antibodies that develop in response to Covid-19 are opsonizing, i.e., they signal to the immune system’s phagocytes to ingest the virus. Our results indicate that non-neutralizing antibodies, so long as they are able to opsonize, are also able to provide an effective response to the virus.”

Pontus Nordenfelt, Researcher, Lund University

Experiments on mice show that non-neutralizing antibodies protect the animals from Covid-19 infection.

The researchers also revealed that the number of neutralizing antibodies had an impact on the phagocytosis process.

Immune system cells were discovered and isolated from the blood of recovered Covid-19 patients. The team found the antibody binding sites and mapped which immune cells interact with the virus’s spike protein using a lot of techniques. Then, they used flow cytometry to investigate how these antibodies impact phagocytosis.

The scientists coated micrometer-sized beads with the spike protein. This enabled them to observe that the dosage of neutralizing antibodies impacted the phagocytosis.

Opsonization is an immune system process that causes a greater phagocyte response when there is an increase in the bound antibodies. Surprisingly, even at low antibody levels, maximal opsonization may be attained. The researchers noticed a decrease in the impact after that. Even though phagocytosis dropped, antibody-binding increased linearly, indicating that the spike protein is responsible for the reduced phagocytosis.

To make sure it is not due to anything else, the researchers repeated the experiment, but this time using monoclonal antibodies alone. This meant that instead of the usual combination of thousands of antibodies, only one kind of antibody (clone) was employed.

It showed the same trend. Up to a certain level, there is a linear dosage effect from the antibodies. After that, it dips. Basically, when you give a dose that is too high you don’t get the protective effect. It looks like something is happening to the spike protein that results in reduced interaction with the white blood cells, leading to the immune system no longer binding to and neutralizing the virus through phagocytosis.”

Wael Bahnan, Study First Author, Researcher, Infection Medicine, Lund University

Similar phenomena have been described as the prozone effect and have been reported in experiments with pneumococcus and malaria. However, it has not been linked to reduced phagocytosis, so it is not certain that the effect relates to what we are observing in our experiments,” remarked Wael Bahnan.

Source:
Journal reference:

Bahnan, W., et al. (2022) Spike-Dependent Opsonization Indicates Both Dose-Dependent Inhibition of Phagocytosis and That Non-Neutralizing Antibodies Can Confer Protection to SARS-CoV-2. Frontiers in Immunology. doi.org/10.3389/fimmu.2021.808932.

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