Distinct immune signatures discriminate SARS-CoV-2 vaccine combinations
Author:
Núñez Nicolás Gonzalo, Schmid Jonas, Power Laura, Alberti Chiara, Krishnarajah Sinduya, Kreutmair Stefanie, Unger Susanne, Blanco Sebastián, Konigheim BrendaORCID, Marín Constanza, Onofrio Luisina, Kienzler Jenny Christine, Costa Pereira Sara da, Ingelfinger Florian, Pasinovich Marina E., Castelli Juan M, Vizzotti Carla, Schaefer Maximilian, Villar-Vesga Juan, Merten Carla Helena, Sethi Aakriti, Wertheimer Tobias, Lutz Mirjam, Vanoaica Danusia, Sotomayor Claudia, Gruppi Adriana, Münz Christian, Cardozo Diego, Barbás Gabriela, Lopez Laura, Carreño Paula, Castro Gonzalo, Raboy Elias, Gallego Sandra, Morón Gabriel, Cervi Laura, Acosta Rodriguez Eva V, Maletto Belkys A, Maccioni Mariana, Becher Burkhard, ,
Abstract
AbstractSeveral vaccines have been found effective against COVID-19, usually administered in homologous regimens, with the same vaccine used for the prime and boost doses. However, recent studies have demonstrated improved protection via heterologous mix-and-match COVID-19 vaccine combinations, and a direct comparison among these regimens is needed to identify the best employment strategies. Here, we show a single-cohort comparison of changes to the humoral and cellular immune compartments following five different COVID-19 vaccines spanning three technologies (adenoviral, mRNA and inactivated vaccines). These vaccines were administered in a combinatorial fashion, resulting in sixteen different homologous and heterologous regimens. SARS-CoV-2-targeting antibody titres were highest when the boost dose consisted of mRNA-1273, independent of the vaccine used for priming. Priming with BBIBP-CorV induced less class-switching among spike-binding memory B cells and the highest antigen-specific T cell responses in heterologous combinations. These were generally more immunogenic in terms of specific antibodies and cellular responses compared to homologous regimens. Finally, single-cell analysis of 754 samples revealed specific B and T cell signatures of the vaccination regimens, indicating distinctive differences in the immune responses. These data provide new insights on the immunological effects of COVID-19 vaccine combinations and a framework for the design of improved vaccination strategies for other pathogens and cancer.
Publisher
Cold Spring Harbor Laboratory
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