García-Pérez, JavierBermejo, MercedesRamírez-García, Almudenade la Torre-Tarazona, Humberto ErickCascajero Díaz, AlmudenaCastillo de la Osa, MaríaJiménez Santana, PalomaAparicio Gómez, MartaCalonge, EstherSancho-López, AránzazuPayares-Herrera, ConcepciónLayunta Acero, RocioVicente-Izquierdo, LauraAvendaño-Solá, CristinaAlcamí, JoséPerez-Olmeda, MayteDíez-Fuertes, Francisco2023-05-172023-05-172023-03J Med Virol. 2023 Mar;95(3):e28679.http://hdl.handle.net/20.500.12105/16083The humoral immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern elicited by vaccination was evaluated in COVID-19 recovered individuals (Rec) separated 1-3 months (Rec2m) or 4-12 months (Rec9m) postinfection and compared to the response in naïve participants. Antibody-mediated immune responses were assessed in 66 participants by three commercial immunoassays and a SARS-CoV-2 lentiviral-based pseudovirus neutralization assay. Immunoglobulin (Ig) levels against SARS-CoV-2 spike were lower in naïve participants after two doses than in Rec after a single dose (p < 0.05). After two doses in Rec, levels of total Ig to receptor-binding domain were significantly increased in Rec9m compared to Rec2m (p < 0.001). The neutralizing potency observed in Rec9m was consistently higher than in Rec2m against variants of concern (VOCs) Alpha, Beta, Delta, and BA.1 sublineage of Omicron with 2.2-2.8-fold increases. Increasing the interval between SARS-CoV-2 infection and the vaccination with messenger RNA-based vaccines to more than 3 months generates a more efficient heterologous humoral immune response against VOCs by allowing enough time to mount a strong recall memory B cell response.engVoRhttp://creativecommons.org/licenses/by/4.0/OmicronHybrid immunitymRNA-1273Neutralizing antibodiesTiming of vaccinationCOVID-19Humans2019-nCoV Vaccine mRNA-1273SARS-CoV-2mRNA VaccinesBiological AssayVaccinationAntibodies, NeutralizingAntibodies, ViralSpike Glycoprotein, CoronavirusAtribución 4.0 Internacional36929737953e2867910.1002/jmv.286791096-9071Journal of medical virologyopen access