Mucosal antibodies in the airways provide durable protection against SARS-CoV-2

High levels of mucosal IgA antibodies in the airways protect against SARS-CoV-2 infection for at least eight months. Omicron infection generates durable mucosal antibodies, reducing the risk of re-infection. These are the findings of a study published in The Lancet Infectious Diseases by researchers at Karolinska Institutet and Danderyd Hospital in Sweden. The results raise further hope for the feasibility of future nasal vaccine platforms to protect against infection.

The COMMUNITY study enrolled 2,149 healthcare workers in the spring of 2020 at Danderyd Hospital, Sweden. Study participants and their immune responses against SARS-CoV-2 have since then been followed through regular samplings from blood and airways along with PCR screenings. A sub-study during January and February 2022 screening 338 triple-vaccinated healthcare workers for SARS-CoV-2 infection found that participants with high (upper quartile) mucosal IgA antibodies in the airways had half the risk of being infected with Omicron compared to those with no or low levels of antibodies in the airways. The researchers have now continued to follow these participants and find the protection to be durable over at least eight months.

90 percent lower risk of re-infection

Participants who were infected with Omicron had a more than 40-fold increase in mucosal IgA antibodies, even if the infection was mild. The current follow-up study now reveals a good durability of these antibodies, and a majority of participants still have protective levels seven months after the infection. Those who were infected with the Omicron variants BA.1 or BA.2 had a 90 percent lower risk of being re-infected with the Omicron variant BA.5.

“Antibodies in the blood protect from severe disease, but if we aim to limit infection, viral transmission and the emergence of new SARS-CoV-2 variants, we need to reinforce our immunity at the mucosal surface, which is the viral point of entry”, says Charlotte Thålin, M.D. and associate professor at the Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet who led the study. “This is not achieved by currently employed intramuscularly-delivered vaccines. But the hope is that a nasal vaccine may generate mucosal immune responses similar to those seen after infection, and thereby block the transmission chain”.

The researchers have also investigated the impact of repeated infections and found that participants with a prior SARS-CoV-2 infection generated a stronger mucosal immune response to Omicron breakthrough infection.

Development of nasal vaccines

“The results show us that it is possible to recall protective and durable mucosal IgA antibody responses in the airways, and that these responses increase with the number of infections. Although these findings are not surprising, they are important for the development of nasal vaccines”, says Ulrika Marking, M.D., PhD student at Karolinska Institutet and first author of the paper.

The COMMUNITY study continues with regular samplings from blood and mucosa, monitoring immune responses after repeated SARS-CoV-2 infections and vaccinations. The study is being conducted in close collaboration between Danderyd Hospital, Karolinska Institutet, Uppsala University, the Public Health Agency of Sweden, KTH Royal Institute of Technology, and SciLifeLab.

The research has been funded by the Jonas and Christina af Jochnick Foundation, the Public Health Agency of Sweden, Region Stockholm, 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.

Publication: “7-month duration of SARS-CoV-2 mucosal immunoglobulin-A responses and protection”. Ulrika Marking, Oscar Bladh, Sebastian Havervall, Julia Svensson, Nina Greilert-Norin, Katherina Aguilera, Martha Kihlgren, Ann-Cristin Salomonsson, Maja Månsson, Radiosa Gallini, Cecilia Kriegholm, Philip Bacchus, Sophia Hober, Max Gordon, Kim Blom, Anna Smed-Sörensen, Mikael Åberg, Jonas Klingström, Charlotte Thålin. The Lancet Infectious Diseases, correspondence, online January 11, 2023, doi: 10.1016/S1473-3099(22)00834-9.