Erice, AlejoErice, AlejoPrieto, LolaCaballero, Cristina2025-11-212025-11-212023-12Erice, A, Prieto, L & Caballero, C 2023, 'Long-Term Analyses of SARS-CoV-2 Humoral and T Cell Responses and Breakthrough SARS-CoV-2 Infections after Two Doses of BNT162b2 Followed by mRNA-1273 and Bivalent Omicron-Adapted BNT162b2 Vaccines : A Prospective Study over 2 Years in Non-Immunocompromised Individuals', Vaccines, vol. 11, no. 12, 1835. https://doi.org/10.3390/vaccines111218352076-393XPubMedCentral: PMC10748336https://hdl.handle.net/10641/6402Publisher Copyright: © 2023 by the authors.Long-term analyses of the immune response following SARS-CoV-2 mRNA vaccines are essential to determining its characteristics and providing the basis for vaccination strategies. We conducted a prospective study in a cohort of 268 healthy adults followed for >2 years after two doses of BNT162b2. Antibodies targeting the receptor-binding domain of the S1 subunit of the spike of SARS-CoV-2 (anti-RBD) were measured at eight time points; T cell response was analyzed using an interferon-γ release assay. A total of 248 (93%) subjects received mRNA-1273 on month 9; 93 (35%) received the bivalent Omicron-adapted BNT162b2 vaccine between months 19 and 26. Breakthrough infections occurred in 215 (80%) participants, with frequencies unaffected by the additional vaccines. Anti-RBD declined over the initial 9 months, increased after mRNA-1273, and declined gradually thereafter. In 50 (17%) previously infected subjects, anti-RBD levels were significantly higher up to month 9 (p < 0.05) but subsequently declined below those of uninfected individuals. Anti-RBD titers protective against SARS-CoV-2 could not be defined. Most subjects developed a positive T cell response that remained after 26 months. Waning of protection against SARS-CoV-2 infection occurred over time, resulting in non-severe breakthrough infections in most participants. The evolution of anti-RBD suggests modulation of the immune response through immune imprinting.1325981enghttp://creativecommons.org/licenses/by-nc-nd/4.0/BNT162b2SARS-CoV-2SARS-CoV-2 T cell responseSARS-CoV-2 antibody humoral immune responseSARS-CoV-2 vaccinebivalent Omicron-adapted vaccineimmune imprintingmRNA-1273ImmunologyPharmacologyDrug DiscoveryInfectious DiseasesPharmacology (medical)SDG 3 - Good Health and Well-beingJournal ArticleYesyesjournal articleopen access10.3390/vaccines11121835https://www.scopus.com/pages/publications/85180707342https://www.scopus.com/pages/publications/85180707342#tab=citedBy