Additional antibodies may protect against COVID, study shows

Date:
January 18, 2022
Source:
Lund University
Summary:
When we talk about antibodies against COVID-19, we tend to mean
the so- called neutralizing antibodies, that offer protection by
blocking the virus from invading our cells. Now, a new study has
revealed that non- neutralizing antibodies may also be important
in providing protection against COVID.



FULL STORY ==========================================================================
When we talk about antibodies against COVID-19, we tend to mean the
so-called neutralising antibodies, that offer protection by blocking the
virus from invading our cells. Now, a new study from Lund University
in Sweden has revealed that non-neutralising antibodies may also be
important in providing protection against Covid.


==========================================================================
"Our results indicate that non-neutralising 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," says Pontus Nordenfelt who led the
study and is a researcher at Lund University.

In its efforts to produce vaccines and treatments, the research community
has focused on neutralising antibodies, which prevent the spike protein
of the virus from binding to the surface protein on our cells.

In a large project led by researchers at Lund University, a more detailed
study has been carried out on how the immune system also fights off the
virus by means of phagocytosis, the ability to ingest foreign particles,
in Covid-19 patients.

Phagocytosis is a type of cleansing mechanism during which the immune
system's players target potential threats, such as bacteria or viruses,
and ingests them, and this mechanism is facilitated if the harmful
substance is marked by an antibody. The results, published in a themed
issue of Frontiers in Immunology,indicate that non-neutralising antibodies
are also important in the fight against Covid -- through this mechanism.

"We observed that many of the antibodies that develop in response
to Covid-19 are opsonising, i.e. they signal to the immune system's
phagocytes to ingest the virus. Our results indicate that non-neutralising antibodies, so long as they are able to opsonise, are also able to
provide an effective response to the virus," says Pontus Nordenfelt.



==========================================================================
The findings are supported by experiments on mice, in which the non- neutralising antibodies protected the animals from Covid-19 infection.

The research team also discovered that the amount of neutralising
antibodies affects the process of phagocytosis.

The team identified and isolated immune system cells from the blood of recovered Covid-19 patients. Using several techniques, they mapped which
immune cells interact with the virus's spike protein and identified the antibody binding sites. Then, using flow cytometry, they studied how
these antibodies affect phagocytosis.

The researchers coated micrometre-sized beads with the spike protein and
in doing so observed that the dosage of neutralising antibodies had an
effect on the phagocytosis.

Opsonisation is the immune system mechanism in which an increase in
bound antibodies triggers a stronger phagocyte response. Surprisingly,
maximum opsonisation is already achieved at relatively low levels of antibodies. Beyond this, the researchers observed a reduction in the
effect. The antibody-binding itself continued to increase linearly,
even when the phagocytosis decreased, demonstrating that it is the spike protein that does something that causes this reduced phagocytosis.

To ensure that this was not due to other factors, the researchers
set up the same experiment, but this time they used only monoclonal
antibodies. This meant that just 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
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,"
says Wael Bahnan, researcher in infection medicine at Lund University
and first author of the study.

"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 neutralising the virus
through phagocytosis. 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," concludes Wael Bahnan.

========================================================================== Story Source: Materials provided by Lund_University. Note: Content may
be edited for style and length.


========================================================================== Journal Reference:
1. Wael Bahnan, Sebastian Wrighton, Martin Sundwall, Anna Bla"ckberg,
Olivia
Larsson, Urban Ho"glund, Hamed Khakzad, Magdalena Godzwon, Maria
Walle, Elisabeth Elder, Anna So"derlund Strand, Lotta Happonen,
Oscar Andre', Johannes Kumra Ahnlide, Thomas Hellmark, Vidar
Wendel-Hansen, Robert PA.

Wallin, Johan Malmsto"m, Lars Malmstro"m, Mats Ohlin, Magnus
Rasmussen, Pontus Nordenfelt. 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, 2022; 12 DOI:
10.3389/fimmu.2021.808932 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220118104128.htm

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