Distinct immune signatures discriminate SARS-CoV-2 vaccine combinations.

NICOLÁS GONZALO NÚÑEZ; JONAS SCHMID, LAURA POWER, CHIARA ALBERTI, SINDUYA KRISHNARAJAH, STEFANIE KREUTMAIR, SUSANNE UNGER, SEBASTIÁN BLANCO3, BRENDA KONIGHEIM, CONSTANZA MARÍN, LUISINA ONOFRIO, JENNY CHRISTINE KIENZLER, SARA DA COSTA PEREIRA, FLORIAN INGELFINGER, ; INMUNOCOVIDCBA: MOTRAN, CLAUDIA C; C VIZZOTTI, M LUTZ, D VANOAICA, C SOTOMAYOR, A GRUPPI, C MÜNZ, D CARDOZO, G BARBÁS, L LOPEZ, P CARREÑO, G CASTRO, E RABOY, S GALLEGO, G MORÓN, L CERVI, E V ACOSTA RODRIGUEZ, B A MALETTO, M MACCIONI, B BECHER.

NATURE IMMUNOLOGY (PRINT)

NATURE PUBLISHING GROUP

Lugar: Londres; Año: 2023

1529-2908

Several 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 thehighest 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.