TY - JOUR

T1 - Diverging humoral and cellular immune responses due to Omicron—a national study from the Faroe Islands

AU - Petersen, Maria Skaalum

AU - Pérez-Alós, Laura

AU - Kongsstovu, Sunnvør K.I.

AU - Eliasen, Eina Hansen

AU - Hansen, Cecilie Bo

AU - Larsen, Sólrun

AU - Hansen, Jóhanna Ljósá

AU - Bayarri-Olmos, Rafael

AU - Fjallsbak, Jógvan Páll

AU - Weihe, Pál

AU - Garred, Peter

N1 - Funding Information: This work was supported by the special COVID-19 funding from the Faroese Research Council; The Carlsberg Foundation (CF20-0045); the Novo Nordisk Foundation (NNF20SA0063180, NFF205A0063505, and NNF20SA0064201); Svend Andersen Research Foundation (SARF2021); the cooperations: Nótaskip, Krúnborg og Borgartún. M.S.P. and P.G. conceptualized and designed the study. S.L. and J.L.H. eligible participants and sent the invitation. M.S.P. was responsible for data collection. E.H.E. prepared the questionnaires in RedCap, and S.K. entered data into REDCap. S.K., J.P.F., L.P-A., C.B.H., and R.B.O. carried out or were responsible for analyses. M.S.P., L.P-A., and C.B.H. carried out the statistical analysis. M.S.P. drafted the version of the manuscript. M.S.P., P.W., and P.G. received funding. All authors reviewed and approved the version. Funding Information: Thanks to all the participants and the technicians drawing the blood samples. Furthermore, thanks to Lina Hansen, research assistant, and the entire Department of Occupational Medicine and Public Health (now Department of Research) staff for assistance throughout the project. The authors would like to thank Mads Engelhardt Knudsen, Sif Kaas Nielsen, Bettina Eide Holm, and Victoria Marie Linderod Larsen from the Laboratory of Molecular Medicine at the Department of Clinical Immunology at Rigshospitalet for their excellent technical assistance. This work was supported by the special COVID-19 funding from the Faroese Research Council; The Carlsberg Foundation (CF20-0045); the Novo Nordisk Foundation (NNF20SA0063180, NFF205A0063505, and NNF20SA0064201); Svend Andersen Research Foundation (SARF2021); the cooperations∶ Nótaskip, Krúnborg og Borgartún. M.S.P. and P.G. conceptualized and designed the study. S.L. and J.L.H. identified eligible participants and sent the invitation. M.S.P. was responsible for data collection. E.H.E. prepared the questionnaires in RedCap, and S.K. entered data into REDCap. S.K., J.P.F., L.P-A., C.B.H., and R.B.O. carried out or were responsible for analyses. M.S.P., L.P-A., and C.B.H. carried out the statistical analysis. M.S.P. drafted the first version of the manuscript. M.S.P., P.W., and P.G. received funding. All authors reviewed and approved the final version. Publisher Copyright: Copyright © 2023 Petersen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

PY - 2023

Y1 - 2023

N2 - Immunity following infection and vaccination with the SARS-CoV-2 Omicron variant is poorly understood. The aim was to investigate immunity assessed with antibody response, neutralizing antibodies (NAbs), and IFN-γ release under different scenarios∶ in vaccinated and unvaccinated individuals with and without SARS-CoV-2 infection with the Omicron variant. This nationwide single-center study was conducted between January and March 2022, where all convalescent individuals were infected with the Omicron variant and included six study groups∶ unvaccinated-naïve, unvaccinated convalescent, vaccinated-naïve (second dose), vaccinated-naïve (third dose), vaccinated convalescent (second dose), and vaccinated convalescent (third dose). Antibody responses were assessed by determining receptor binding domain-specific antibodies and NAbs levels in serum, and IgG in saliva. T-cell responses in whole blood were measured as IFN-γ levels released after stimulation with spike peptides. We found that the humoral response against the spike protein was higher among vaccinated-naïve than unvaccinated convalescent. Unvaccinated with and without infection had comparable low humoral responses, while those vaccinated with a second or third dose, independent of infection status, had increasingly higher levels. Only 22% of the unvaccinated convalescent individuals mounted consistent detectable humoral responses following Omicron infection. However, 98% had spike peptide T-cell responses assessed by IFN-γ release. In conclusion, primary Omicron infection mounts a low humoral immune response, significantly enhanced by prior vaccination. Omicron infection induced a robust T-cell response in both unvaccinated and vaccinated, demonstrating that the evasive immune potential of primary Omicron infection affects humoral immunity more significantly than T-cell immunity.

AB - Immunity following infection and vaccination with the SARS-CoV-2 Omicron variant is poorly understood. The aim was to investigate immunity assessed with antibody response, neutralizing antibodies (NAbs), and IFN-γ release under different scenarios∶ in vaccinated and unvaccinated individuals with and without SARS-CoV-2 infection with the Omicron variant. This nationwide single-center study was conducted between January and March 2022, where all convalescent individuals were infected with the Omicron variant and included six study groups∶ unvaccinated-naïve, unvaccinated convalescent, vaccinated-naïve (second dose), vaccinated-naïve (third dose), vaccinated convalescent (second dose), and vaccinated convalescent (third dose). Antibody responses were assessed by determining receptor binding domain-specific antibodies and NAbs levels in serum, and IgG in saliva. T-cell responses in whole blood were measured as IFN-γ levels released after stimulation with spike peptides. We found that the humoral response against the spike protein was higher among vaccinated-naïve than unvaccinated convalescent. Unvaccinated with and without infection had comparable low humoral responses, while those vaccinated with a second or third dose, independent of infection status, had increasingly higher levels. Only 22% of the unvaccinated convalescent individuals mounted consistent detectable humoral responses following Omicron infection. However, 98% had spike peptide T-cell responses assessed by IFN-γ release. In conclusion, primary Omicron infection mounts a low humoral immune response, significantly enhanced by prior vaccination. Omicron infection induced a robust T-cell response in both unvaccinated and vaccinated, demonstrating that the evasive immune potential of primary Omicron infection affects humoral immunity more significantly than T-cell immunity.

KW - cellular immune response

KW - Faroe Islands

KW - humoral immune response

KW - Omicron

U2 - 10.1128/spectrum.00865-23

DO - 10.1128/spectrum.00865-23

M3 - Journal article

C2 - 37909772

AN - SCOPUS:85180012862

VL - 11

JO - Microbiology spectrum

JF - Microbiology spectrum

SN - 2165-0497

IS - 6

ER -