Tejedor Vaquero, Sonia, 1988-Campos Mata, Leire de, 1991-Ramada Rodilla, José María, 1961-Díaz, PilarNavarro-Barriuso, JuanRibas-Llauradó, ClaraRodrigo Melero, NataliaCarolis, CarloCerutti, Andrea, 1965-Gimeno Martínez, RamónMagri, Giuliana, 1978-2022-01-192022-01-192021Tejedor Vaquero S, de Campos-Mata L, Ramada JM, Díaz P, Navarro-Barriuso J, Ribas-Llaurado C et al. The mRNA-1273 vaccine induces cross-variant antibody responses to SARS-CoV-2 with distinct profiles in individuals with or without pre-existing immunity. Front Immunol. 2021;12:737083. DOI: 10.3389/fimmu.2021.7370831664-3224http://hdl.handle.net/10230/52261mRNA-based vaccines effectively induce protective neutralizing antibodies against SARS-CoV-2, the etiological agent of COVID-19. Yet, the kinetics and compositional patterns of vaccine-induced antibody responses to the original strain and emerging variants of concern remain largely unknown. Here we characterized serum antibody classes and subclasses targeting the spike receptor-binding domain of SARS-CoV-2 wild type and α, β, γ and δ variants in a longitudinal cohort of SARS-CoV-2 naïve and COVID-19 recovered individuals receiving the mRNA-1273 vaccine. We found that mRNA-1273 vaccine recipients developed a SARS-CoV-2-specific antibody response with a subclass profile comparable to that induced by natural infection. Importantly, these antibody responses targeted both wild type SARS-CoV-2 as well as its α, β, γ and δ variants. Following primary vaccination, individuals with pre-existing immunity showed higher induction of all antibodies but IgG3 compared to SARS-CoV-2-naïve subjects. Unlike naïve individuals, COVID-19 recovered subjects did not mount a recall antibody response upon the second vaccine dose. In these individuals, secondary immunization resulted in a slight reduction of IgG1 against the receptor-binding domain of β and γ variants. Despite the lack of recall humoral response, vaccinees with pre-existing immunity still showed higher titers of IgG1 and IgA to all variants analyzed compared to fully vaccinated naïve individuals. Our findings indicate that mRNA-1273 vaccine triggered cross-variant antibody responses with distinct profiles in vaccinees with or without pre-existing immunity and suggest that individuals with prior history of SARS-CoV-2 infection may not benefit from the second mRNA vaccine dose with the current standard regimen.application/pdfeng© 2021 Sonia Tejedor Vaquero et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these termsCOVID-19 (Malaltia)VacunacióImmunitatinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3389/fimmu.2021.737083info:eu-repo/semantics/openAccess