High-dimensional analysis of sixteen SARS-COV-2 vaccine combinations reveals lymphocyte signature correlating with immunogenicity.

NICOLÁS NÚÑEZ, JONAS SCHMID, LAURA POWER, CHIARA ALBERTI, SINDUYA KRISHNARAJAH, STEFANIE KREUTMAIR, SUSANNE UNGER, SEBASTIÁN BLANCO, BRENDA KONIGHEIM, CONSTANZA MARÍN, LUISINA ONOFRIO, JENNY CHRISTINE KIENZLER, SARA DA COSTA PEREIRA, FLORIAN INGELFINGER,; CERBAN, FABIO, INMUNOCOVIDCBA: LAURA CHIAPELLO PHD, CAROLINA MONTES PHD, CRISTINA MOTRÁN PHD, JEREMÍAS DUTTO, LAURA ALMADA, AND LUCÍA BOFFELLI; INVIV WORKING GROUP: LORENA SPINSANTI PHD, ADRIÁN DÍAZ PHD, MARÍA ELISA RIVAROLA PHD, JAVIER AGUILAR BIOQ., AND MAURICIO BERANEK PHD; MARINA E. PASINOVICH, JUAN M CASTELLI, CARLA VIZZOTTI, MAXIMILIAN SCHAEFER, JUAN VILLAR-VESGA, CARLA HELENA MERTEN, AAKRITI SETHI, TOBIAS WERTHEIMER, MIRJAM LUTZ, DANUSIA VANOAICA, CLAUDIA SOTOMAYOR, ADRIANA GRUPPI, CHRISTIAN MÜNZ,; DIEGO CARDOZO, GABRIELA BARBÁS, LAURA LOPEZ, PAULA CARREÑO, GONZALO CASTRO, ELIAS RABOY, SANDRA GALLEGO,; GABRIEL MORÓN, LAURA CERVI, EVA V ACOSTA RODRIGUEZ, BELKYS A MALETTO, MARIANA MACCIONI, BURKHARD BECHER.

NATURE IMMUNOLOGY (PRINT)

NATURE PUBLISHING GROUP

Año: 2023

1529-2908

Several vaccines have been found effective against COVID-19, usually administered inhomologous regimens, with the same vaccine used for the prime and boost doses. However,recent studies have demonstrated improved protection via heterologous mix-and-matchCOVID-19 vaccine combinations, and a direct comparison among these regimens is needed toidentify the best employment strategies. Here, we show a single-cohort comparison of changesto the humoral and cellular immune compartments following five different COVID-19 vaccinesspanning three technologies (adenoviral, mRNA and inactivated vaccines). These vaccines wereadministered in a combinatorial fashion, resulting in sixteen different homologous andheterologous regimens. SARS-CoV-2-targeting antibody titres were highest when the boostdose consisted of mRNA-1273, independent of the vaccine used for priming. Priming withBBIBP-CorV induced less class-switching among spike-binding memory B cells and the highestantigen-specific T cell responses in heterologous combinations. These were generally moreimmunogenic 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 signaturesof the vaccination regimens, indicating distinctive differences in the immune responses. Thesedata provide new insights on the immunological effects of COVID-19 vaccine combinations anda framework for the design of improved vaccination strategies for other pathogens and cancer.