High-dimensional analysis of 16 SARS-CoV-2 vaccine combinations reveals lymphocyte signatures correlating with immunogenicity
Nicolás Gonzalo Núñez, Jonas Schmid, Laura Power, Chiara Alberti, Sinduya Krishnarajah, Stefanie Kreutmair, Susanne Unger, Sebastián Blanco, Brenda Konigheim, Constanza Marín, Luisina I. Onofrio, Jenny C. Kienzler, Sara Costa-Pereira, Florian Ingelfinger, InmunoCovidCba, Fabio M. Cerbán, Laura S. Chiapello, Carolina L. Montes, Claudia Cristina Motrán, Jeremías Dutto, Laura Almada, Lucía Boffelli, InViV working group, Lorena Spinsanti, Adrián Díaz, María Elisa Rivarola, Javier Aguilar Bioq, Mauricio Beranek, Marina Pasinovich, Juan Manuel Castelli, Carla Vizzotti, Maximilian Schaefer, Juan Villar-Vesga, Sarah Mundt, Carla Helena Merten, Aakriti Sethi, Tobias Wertheimer, Mirjam Lutz, Danusia Vanoaica, Claudia Elena Sotomayor, Adriana Gruppi, Christian Münz, Diego Cardozo, Gabriela Barbás, Laura López, Paula Carreño, Gonzalo Castro, Elias Raboy, Sandra Gallego, Gabriel Morón, Laura Cervi, Eva V. Acosta Rodríguez, Belkys Maletto, Mariana Maccioni, Burkhard Becher
Abstract
The range of vaccines developed against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) provides a unique opportunity to study immunization across different platforms. In a single-center cohort, we analyzed the humoral and cellular immune compartments following five coronavirus disease 2019 (COVID-19) vaccines spanning three technologies (adenoviral, mRNA and inactivated virus) administered in 16 combinations. For adenoviral and inactivated-virus vaccines, heterologous combinations were generally more immunogenic compared to homologous regimens. The mRNA vaccine as the second dose resulted in the strongest antibody response and induced the highest frequency of spike-binding memory B cells irrespective of the priming vaccine. Priming with the inactivated-virus vaccine increased the SARS-CoV-2-specific T cell response, whereas boosting did not. Distinct immune signatures were elicited by the different vaccine combinations, demonstrating that the immune response is shaped by the type of vaccines applied and the order in which they are delivered. These data provide a framework for improving future vaccine strategies against pathogens and cancer.