High-dimensional analysis of sixteen SARS-CoV-2 vaccine combinations reveals lymphocyte signatures correlating with immunogenicity

NICOLAS NUÑEZ; JONAS SCHMID; LAURA POWER; CHIARA ALBERTI; SINDUYA KRISHNARAJAH; STEFANIE KREUTMAIR; SUSANNE UNGER; SEBASTIÁN BLANCO; BRENDA KONIGHEIM; CONSTANZA MARIN; LUISINA ONOFRIO; JENNY CHRISTINE KIENZLER; SARA DA COSTA PEREIRA; FLORIAN INGELFINGER; GRUPO INMUNOCOVIDCBA; MARINA E. PASINOVICH; JUAN M CASTELLI; CARLA VIZZOTTI; MAXIMILIAN SCHAEFER; JUAN VILLAR-VESGA; SARAH MUNDT; 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*; MACCIONI, MARIANA*; BURKHARD BECHER*

NATURE IMMUNOLOGY (PRINT)

NATURE PUBLISHING GROUP

Lugar: Londres; Año: 2023

1529-2908

The COVID-19 pandemicled to the development of a broad range of vaccines against SARS-CoV-2. Thisoffers a unique opportunity to study the human immune response to differenttypes of vaccines and their heterologous combinations. Here, we show asingle-cohort characterisation of changes to the humoral and cellular immunecompartments following five different COVID-19 vaccines spanning three technologies(adenoviral, mRNA and inactivated vaccines). These vaccines were administeredin a combinatorial fashion, resulting in sixteen different homologous andheterologous regimens. Single-cell analysis of 754 samples revealed thatpriming with the inactivated-virus vaccine BBIBP-CorV induced lessclass-switching among spike-binding memory B cells and led to a higherfrequency of CD4-CD8- T cell clusters as well as thehighest antigen-specific T cell responses. In contrast, BBIBP-CorV administeredas a second dose (a scheme proved to induce a poor antibody response) elicitedspike-binding memory B cells that were CD21hiCD38hiCXCR5hi.Furthermore, spike-specific memory B cells with an activated (CD21-CD38-/low)phenotype and a CXCR5loCXCR3hiIgA+ expressionprofile were associated with higher antibody titers and a stronger serumneutralizing activity. These data provide new insights on the cellular effectsof different vaccine types and a framework for the design of improvedvaccination strategies against pathogens and cancer@font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:roman;mso-font-pitch:variable;mso-font-signature:-536870145 1107305727 0 0 415 0;}p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin:0cm;line-height:115%;mso-pagination:widow-orphan;font-size:11.0pt;font-family:"Arial",sans-serif;mso-fareast-font-family:Arial;mso-ansi-language:#0007;mso-fareast-language:DE-CH;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-size:11.0pt;mso-ansi-font-size:11.0pt;mso-bidi-font-size:11.0pt;font-family:"Arial",sans-serif;mso-ascii-font-family:Arial;mso-fareast-font-family:Arial;mso-hansi-font-family:Arial;mso-bidi-font-family:Arial;mso-ansi-language:#0007;mso-fareast-language:DE-CH;}.MsoPapDefault{mso-style-type:export-only;line-height:115%;}div.WordSection1{page:WordSection1;}