02 May 2024

Researchers at BKV have participated in a large study in which an international research team has shown that IgA antibodies in the nasal mucosa can protect against infection with SARS-Cov-2. The study was conducted on mice and led by researchers at Karolinska Institutet. Their results were recently published in the journal PNAS.

 

Door to biosafety laboratory.
The SARS-Cov-2 trials are conducted in a biosafety level 3 (out of 4) laboratory at LiUThor Balkhed

The vaccines against COVID-19, taken by a large part of the population, provide so-called immunological protection. This type of protection reduces the risk of becoming seriously ill from an infection, but does not protect against infection.

Headshot of man wearing lab coat.
Lennart Svensson, professor at Linköping University.Thor Balkhed

“Many people confuse protection against infection with protection against disease. It’s very difficult to provide protection that prevents viruses or bacteria from infecting us. That’s the kind of protection that allows us to gain herd immunity in society, so that a certain virus doesn’t manage to spread. We don’t develop herd immunity after SARS-coV-2 vaccination,” says Lennart Svensson, professor of virology at BKV.

However, some particularly sensitive groups could benefit from protection from being infected by SARS-CoV-2 at all. It is such protection against infection that researchers wanted to achieve in a large Swedish-Chinese research collaboration. The researchers have explored a new way to protect particularly vulnerable individuals, such as people with a compromised immune system or the elderly, against different variants of the virus.

IgA antibodies first to meet the virus

Most often when we think of protection against infections, we mean antibodies of the IgG type, which are found in the blood. But there are others too. IgA antibodies are found on all mucous membranes, for example in the nose and intestines. They are part of the body’s first protection against viruses and bacteria. Should harmful microorganisms manage to penetrate this defence and spread via the blood, IgG antibodies can take over the defence.

In the current study published in PNAS, researchers have converted IgG antibodies into IgA antibodies that could be administered in the form of a nasal spray. But why turn one type of antibody into another?

As there are more IgG antibodies than IgA antibodies, it is easier to find antibodies of the IgG type that can recognise SARS-coV-2. The researchers in the study began by identifying and purifying such specific IgG antibodies. A research team at Karolinska Institutet then converted them into IgA antibodies using genetic engineering.

Prevented the virus from infecting

In the study, Marie Hagbom and Lennart Svensson tested the ability of the synthetic antibodies to prevent SARS-CoV-2 infection in cells. Antibody protection was also studied in mice, where they were administered via nasal drops. It was found that this way of supplying the antibodies provided protection against infection as well as therapeutic protection.

Headshot of woman wearing lab coat.
Marie Hagbom, docent at Linköping University.Thor Balkhed

“The most important findings in the study are that these IgA antibodies have been successfully constructed from IgG antibodies and that the IgA antibodies provide protection against SARS-CoV-2 infection in an experimental animal model. This has never been done before. Since they were produced synthetically, it’s possible to make such antibodies on a large scale in a laboratory. The study has opened a door in research to learn how to use molecular genetic methods to create antibodies that protect against infection,” says Lennart Svensson.

The study can be seen as a first step, and it will take many years before it is possible to treat people with IgA antibodies in the way the researchers explored in the study.

“A nasal spray with IgA antibodies may possibly serve as protection for certain high-risk individuals. But we also need to understand how the body’s IgA protection works,” says Docent Marie Hagbom, also at BKV.

The study was led by researchers at Karolinska Institutet and was conducted within the European research consortium ATAC. The research was funded by the EU’s Horizon 2020 research and innovation programme, a joint Swedish-Chinese (VR-NCSF) grant, the Knut and Alice Wallenberg Foundation and the Swiss National Science Foundation (BRIDGE). Some of the researchers have patents relating to antibody treatment.

Article: Conversion of monoclonal IgG to dimeric and secretory IgA stores neutralizing ability and prevents infection of Omicron, Harold Marcotte, Yunlong Cao, Fanglei Zuo, et al. PNAS. Published online 9 January 2024, doi:10.1073/pnas.2315354120

Translation by Anneli Mosell

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