AUTHOR=Horndler Lydia , Delgado Pilar , Romero-Pinedo Salvador , Quesada Marina , Balabanov Ivaylo , Laguna-Goya Rocío , Almendro-Vázquez Patricia , Llamas Miguel A. , Fresno Manuel , Paz-Artal Estela , van Santen Hisse M. , Álvarez-Fernández Stela , Olmo Asunción , Alarcón Balbino TITLE=Decreased breadth of the antibody response to the spike protein of SARS-CoV-2 after repeated vaccination JOURNAL=Frontiers in Immunology VOLUME=Volume 14 - 2023 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1157263 DOI=10.3389/fimmu.2023.1157263 ISSN=1664-3224 ABSTRACT=The rapid development of vaccines to prevent infection by SARS-CoV-2 virus causing COVID-19 makes necessary to compare the capacity of the different vaccines in terms of development of a protective humoral response. Here, we have used a highly sensitive and reliable flow cytometry method to measure the titers of antibodies of the IgG1 isotype in blood of healthy volunteers after receiving one or two doses of the vaccines being administered in Spain. We took advantage of the multiplexed capacity of the method to measure simultaneously the reactivity of antibodies with the S protein of the original strain Wuhan and the variants B.1.1.7 (Alpha), B.1.617.2 (Delta) and B.1.617.1 (Kappa). We found significant differences in the titer of anti-S antibodies produced after a first dose of the vaccines ChAdOx1 nCov-19/AstraZeneca, mRNA-1273/Moderna, BNT162b2/Pfizer-BioNTech and Ad26.COV.S/Janssen. Most important, we found a relative reduction in the reactivity of the sera with the Alpha, Delta and Kappa variants, versus the Wuhan one, after the second boosting immunization. These data allow to make a comparison of different vaccines in terms of anti-S antibody generation and cast doubts about the convenience of repeatedly immunizing with the same S protein sequence.