Frontiers in Immunology (Nov 2024)

Unbiased immunome characterisation correlates with COVID-19 mRNA vaccine failure in immunocompromised adults

  • Juan H-Vázquez,
  • Paloma Cal-Sabater,
  • Elisa Arribas-Rodríguez,
  • Aida Fiz-López,
  • Candido Perez-Segurado,
  • Álvaro Martín-Muñoz,
  • Ángel De Prado,
  • Marina Perez Mazzali,
  • Carolina G. de Castro,
  • Alejandro G. del Hierro,
  • Ignacio de la Fuente Graciani,
  • Sonia Pérez González,
  • Sara Gutiérrez,
  • Pablo Tellería,
  • Cristina Novoa,
  • Silvia Rojo Rello,
  • Antonio Garcia-Blesa,
  • Rosa Sedano,
  • Ana María Martínez García,
  • Sonsoles Garcinuño Pérez,
  • Marta Domínguez-Gil,
  • Cristina Hernán García,
  • Ma Mercedes Guerra,
  • Eduardo Muñoz-Sánchez,
  • Cristina Barragan-Pérez,
  • Soraya Diez Morales,
  • Oriana Casazza Donnarumma,
  • Daniel Ramos Pollo,
  • Natalia Santamarta Solla,
  • Paula Ma Álvarez Manzanares,
  • Sara Bravo,
  • Cristina García Alonso,
  • Luis Alberto Avendaño Fernández,
  • Jenifer Gay Alonso,
  • José A. Garrote,
  • Eduardo Arranz,
  • José María Eiros,
  • Fernando Rescalvo Santiago,
  • Carolina Quevedo Villegas,
  • Eduardo Tamayo,
  • Eduardo Tamayo,
  • Antonio Orduña,
  • Carlos Dueñas,
  • María Jesús Peñarrubia,
  • Sara Cuesta-Sancho,
  • María Montoya,
  • David Bernardo,
  • David Bernardo

DOI
https://doi.org/10.3389/fimmu.2024.1405217
Journal volume & issue
Vol. 15

Abstract

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IntroductionCoronavirus disease 2019 (COVID-19) affects the population unequally, with a greater impact on older and immunosuppressed people.MethodsHence, we performed a prospective experimental cohort study to characterise the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in immune-compromised patients (older adults and oncohaematologic patients), compared with healthy counterparts, based on deep characterisation of the circulating immune cell subsets.Results and discussionWhile acquired humoral and cellular memory did not predict subsequent infection 18 months after full vaccination, spectral and computational cytometry revealed several subsets within the CD8+ T-cells, B-cells, natural killer (NK) cells, monocytes and TEMRA Tγδ cells that were differentially expressed in individuals who were subsequently infected and not infected not just following immunisation, but also prior to vaccination. Of note, we found up to seven clusters within the TEMRA Tγδ cell population, with some of them being expanded and others decreased in subsequently infected individuals. Moreover, some of these cellular clusters were also related to COVID-19-induced hospitalisation in oncohaematologic patients. Therefore, we have identified a cellular signature that even before vaccination is related to COVID-19 vulnerability as opposed to the acquisition of cellular and/or humoral memory following vaccination with SARS-CoV-2 messenger RNA (mRNA) vaccines.

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