{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T01:02:28Z","timestamp":1769043748497,"version":"3.49.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T00:00:00Z","timestamp":1679443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>SARS-CoV-2 vaccination is the leading strategy to prevent severe courses after SARS-CoV-2 infection. In our study, we analyzed humoral and cellular immune responses in detail to three consecutive homologous or heterologous SARS-CoV-2 vaccinations and breakthrough infections.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Peripheral blood samples of n=20 individuals were analyzed in the time course of three SARS-CoV-2 vaccinations and\/or breakthrough infection. S1-, RBD-, S2- and N-specific IgG antibodies were quantified using Luminex-based multiplex assays and electrochemiluminescence multiplex assays for surrogate neutralization in plasma. Changes in cellular immune components were determined via flow cytometry of whole blood samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All individuals (n=20) responded to vaccination with increasing S1-\/RBD-\/S2-specific IgG levels, whereas specific plasma IgA displayed individual variability. The third dose increased antibody inhibitory capacity (AIC) against immune-escape variants Beta and Omicron BA.1 independently of age. The mRNA-primed vaccination induced IgG and IgA immunity more efficiently, whereas vector-primed individuals displayed higher levels of memory T and B cells. Vaccinees showed SARS-CoV-2-specific T cell responses, which were further improved and specified after Omicron breakthrough infections in parallel to the appearance of new variant-specific antibodies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>In conclusion, the third vaccination was essential to increase IgG levels, mandatory to boost AIC against immune-escape variants, and induced SARS-CoV-2-specific T cells. Breakthrough infection with Omicron generates additional spike specificities covering all known variants.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1120010","type":"journal-article","created":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T05:43:55Z","timestamp":1679463835000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Third SARS-CoV-2 vaccination and breakthrough infections enhance humoral and cellular immunity against variants of concern"],"prefix":"10.3389","volume":"14","author":[{"given":"Louisa","family":"Ruhl","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny 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