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

• Published in: Microbiology Spectrum
• Main Authors: Petersen, Maria Skaalum, Pérez-Alós, Laura, Kongsstovu, Sunnvør K.I., Eliasen, Eina Hansen, Hansen, Cecilie Bo, Larsen, Sólrun, Hansen, Jóhanna Ljósá, Bayarri-Olmos, Rafael, Fjallsbak, Jógvan Páll, Weihe, Pál, Garred, Peter
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2023
• Subjects: cellular immune response; Faroe Islands; humoral immune response; Omicron; The Spike
• Online Access: https://curis.ku.dk/portal/da/publications/diverging-humoral-and-cellular-immune-responses-due-to-omicrona-national-study-from-the-faroe-islands(c199a6d2-b402-48b6-bd42-479b019cc400).html; https://doi.org/10.1128/spectrum.00865-23; https://curis.ku.dk/ws/files/396014328/petersen_et_al_2023_diverging_humoral_and_cellular_immune_responses_due_to_omicron_a_national_study_from_the_faroe.pdf

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.