Cell Reports (Apr 2025)

Long-lasting antibody B-cell responses to SARS-CoV-2 three years after the onset of the pandemic

  • Luis M. Molinos-Albert,
  • Rocío Rubio,
  • Carla Martín-Pérez,
  • Edwards Pradenas,
  • Cèlia Torres,
  • Alfons Jiménez,
  • Mar Canyelles,
  • Marta Vidal,
  • Diana Barrios,
  • Silvia Marfil,
  • Ester Aparicio,
  • Anna Ramírez-Morros,
  • Benjamin Trinité,
  • Josep Vidal-Alaball,
  • Pere Santamaria,
  • Pau Serra,
  • Luis Izquierdo,
  • Ruth Aguilar,
  • Anna Ruiz-Comellas,
  • Julià Blanco,
  • Carlota Dobaño,
  • Gemma Moncunill

Journal volume & issue
Vol. 44, no. 4
p. 115498

Abstract

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Summary: Immune memory is essential for the effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. In the current context of the pandemic, with a diminished vaccine efficacy against emerging variants, it remains crucial to perform long-term studies to evaluate the durability and quality of immune responses. Here, we examined the antibody and memory B-cell responses in a cohort of 113 healthcare workers with distinct exposure histories over a 3-year period. Previously infected and naive participants developed comparable humoral responses by 17 months after receiving a full three-dose mRNA vaccination. In addition, both maintained a substantial SARS-CoV-2-reactive memory B-cell pool, associated with a lower incidence of breakthrough infections in naive participants. Of note, previously infected participants developed an expanded SARS-CoV-2-reactive CD27−CD21− atypical B-cell population that remained stable throughout the follow-up period. Thus, previous SARS-CoV-2 infection differentially imprints the memory B-cell compartment without compromising the development of long-lasting humoral responses.

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