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

ICOLÁS GONZALO N U ÑEZ, JONAS SCHMID , LAURA POWER; SEBASTIÁN BLANCO, BRENDA KONIGHEIM, CONSTANZA MARÍN , LUISINA ONOFRIO; NMUNOCOVIDCBA, INVIV WORKING GROUP; MARINA E. PASINOVICH , JUAN M CASTELLI , CARLA VIZZOTTI; LAUDIA SOTOMAYOR , ADRIANA GRUPPI; DIEGO CARDOZO , GABRIELA BARBÁS 2 , LAURA LOPEZ 2 , PAULA CARREÑO , GONZALO CASTRO , ELIAS RABOY; MARIANA MACCIONI; BURKHARD BECHER

NATURE IMMUNOLOGY (PRINT)

NATURE PUBLISHING GROUP

Lugar: Londres; Año: 2023

1529-2908

The COVID-19 pandemic has led to the development of a broad range of vaccines, providing a unique opportunity to study immunization across different platforms. In a single cohort, we analyzed the humoral and cellular immune compartments following five COVID-19 vaccines spanning three technologies (adenoviral, mRNA, and inactivated-virus) administered combinatorially, resulting in 16 homologous and heterologous regimens. For non-mRNA vaccines, heterologous combinations were generally more immunogenic in terms of specific antibody and cellular responses compared to homologous regimens. Quantification of serum antibodies and single-cell analysis revealed that the strongest antibody response and the highest frequency of spike-binding memory B cells (mBCs) was achieved when the second dose consisted of the mRNA-based vaccine. Priming with the inactivated-virus vaccine BBIBP-CorV potently induced IgA antibody production in heterologous combinations, increased IgM expression among spike-binding mBCs and led to the highest frequency of a CD4-CD8- T cell subset as well as antigen-specific T cell responses. In contrast, BBIBP-CorV administered as a second dose induced a poor antibody response and was characterized by CD21hiCD38hiCXCR5hi spike-binding memory B cells. Furthermore, activated CD21-CD38-/low and CXCR5loCXCR3hiIgA+ spike-specific memory B cells were associated with higher antibody titres and more serum neutralizing activity. These data provide new insights into the cellular effects of different vaccine types and a framework for improving future vaccine strategies against pathogens and cancer.