Mucosal antibodies protect the airways

High levels of mucosal antibodies in the airways reduce the risk of omicron infection, but many do not receive detectable antibodies in the airways despite three doses of the SARS-CoV-2 vaccine. These are the results of a study published today in The New England Journal of Medicine, Led by researchers at Karolinska Institutet and Danderyd Hospital in Sweden.

The COMMUNITY study enrolled 2,149 healthcare workers in the spring of 2020 at Danderyd Hospital, Sweden. Since then, study participants and their immune responses to SARS-CoV-2 have been monitored every four months. A substudy between January and February 2022 screened 338 healthcare workers who were triple vaccinated for SARS-CoV-2 infection. Antibody levels in the blood and airways were determined at the beginning of the examination period, and one in six (57 participants) subsequently developed omicron during the four-week examination period. This allowed the research group to investigate immunity against omicron penetrating infection as well as boosting immunity after penetrating infection.

Levels of mucosal IgA antibodies (immunoglobulin A) were measured in the airways because they play an important role in protecting against respiratory infections. All participants had high levels of systemic antibodies (eg in the blood) after three doses of the vaccine, but only 62 percent had detectable antibodies in the mucous membranes (eg in the nose). High levels of antibodies in the mucosal airway cut the risk of omicron infection in half.

“It is not surprising that antibodies in the respiratory tract locally neutralize the virus, but these results show, for the first time, that mucosal antibodies to SARS-CoV-2 in the airways actually protect against oomicron infection,” says lead author Charlotte Thalin, MD and Associate Professor in the Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet.

Higher mucosal antibodies in the airways were also associated with lower viral replication among those with omicrons. After omicron infection, a 40-fold increase in airway mucosal antibodies was found in the majority of participants, even if the infection was mild.

The researchers also showed that participants with SARS-CoV-2 infection before vaccination had significantly higher levels of antibodies in the post-vaccination mucosal airway compared to the triple vaccination with no previous SARS-CoV-2 infection. This may explain why so-called hybrid immunity, a combination of infection and a vaccine, provides stronger protection against infection than just vaccines.

“We are now in a situation with people getting omicron despite having received multiple doses of current intramuscular vaccines,” says Charlotte Thalin. “It is tempting to think that a nasal or orally administered vaccine, where SARS-CoV-2 enters the body, can provoke a local immune response that prevents infection at an early stage. Several vaccines in the form of a nasal spray are now being investigated in Clinical trials are hoping to be able to reduce the spread of infection and thus reduce the risk of developing new viral variants.

The COMMUNITY study continues with regular blood and mucosal sampling, and monitoring of immune responses following repeated SARS infections and vaccinations. The study was conducted in close collaboration between Danderyd Hospital, Karolinska Institutet, Uppsala University, the Swedish Public Health Agency, KTH Royal Institute of Technology and SciLifeLab.

The research was funded by the Jonas and Christina af Jochnick Foundation, Stockholm Region, the Knut and Alice Wallenberg Foundation, Leif Lundblad and Family, the Swedish Research Council, the Swedish Heart-Lung Foundation, the Bill and Melinda Gates Foundation, Karolinska Institutet and SciLifeLab.

the post: “Anti-Spike Mucosal IgA Protection Against SARS-CoV-2 Omicron Infection,” Sebastian Havervall, Ulrika Marking, Julia Svensson, Nina Greilert Norin, Philip Bacchus, Peter Nilsson, Sophia Hober, Max Gordon, Kim Blom, Jonas Klingström, Mikael , Anna Smid Sorensen, Charlotte Thalin. The New England Journal of Medicine (NEJM)Letter to the Editor, Online Sep 14, 2022, doi: 10.1056/NEJMc2209651.


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