Luczkowiak, JoannaRivas, GonzaloLabiod, NuriaLasala, FátimaRolo, MartaLora-Tamayo Morillo-Velarde, JaimeMancheno Losa, MikelRial Crestelo, DavidPérez Rivilla, José AlfredoFolgueira López, María DoloresDelgado Vázquez, Rafael2023-06-222023-06-222023-11-010146-661510.1002/jmv.28268https://hdl.handle.net/20.500.14352/72699CRUE-CSIC (Acuerdos Transformativos 2022)We have measured the humoral response to messenger RNA (mRNA) vaccines in COVID-19 naïve and convalescent individuals. Third doses of mRNA COVID-19 vaccines induced a significant increase in potency and breadth of neutralization against SARS-CoV-2 variants of concern (VoC) including Omicron subvariants BA.1, BA.2, and BA.2.12.1, that were cross-neutralized at comparable levels and less for BA.4/5. This booster effect was especially important in naïve individuals that only after the third dose achieved a level that was comparable with that of vaccinated COVID-19 convalescents except for BA.4/5. Avidity of RBD-binding antibodies was also significantly increased in naïve individuals after the third dose, indicating an association between affinity maturation and cross neutralization of VoC. These results suggest that at least three antigenic stimuli by infection or vaccination with ancestral SARS-CoV-2 sequences are required to induce high avidity cross-neutralizing antibodies. Nevertheless, the circulation of new subvariants such as BA.4/5 with partial resistance to neutralization will have to be closely monitored and eventually consider for future vaccine developments.engAtribución-NoComercial-SinDerivadas 3.0 Españahttps://creativecommons.org/licenses/by-nc-nd/3.0/es/journal articlehttps://doi.org/10.1002/jmv.28268open accessavidityCOVID‐19neutralizing antibodiesOmicronSARS‐CoV‐2vaccinesvariants of concernInmunología2412 Inmunología