The magnitude and timing of recalled immunity after breakthrough infection is shaped by SARS-CoV-2 variants

Marios Koutsakos, Wen Shi Lee, Arnold Reynaldi, Hyon Xhi Tan, Grace Gare, Paul Kinsella, Kwee Chin Liew, George Taiaroa, Deborah A. Williamson, Helen E. Kent, Eva Stadler, Deborah Cromer, David S. Khoury, Adam K. Wheatley, Jennifer A. Juno, Miles P. Davenport, Stephen J. Kent

Research output: Contribution to journalArticleResearchpeer-review

34 Citations (Scopus)

Abstract

Vaccination against SARS-CoV-2 protects from infection and improves clinical outcomes in breakthrough infections, likely reflecting residual vaccine-elicited immunity and recall of immunological memory. Here, we define the early kinetics of spike-specific humoral and cellular immunity after vaccination of seropositive individuals and after Delta or Omicron breakthrough infection in vaccinated individuals. Early longitudinal sampling revealed the timing and magnitude of recall, with the phenotypic activation of B cells preceding an increase in neutralizing antibody titers. While vaccination of seropositive individuals resulted in robust recall of humoral and T cell immunity, recall of vaccine-elicited responses was delayed and variable in magnitude during breakthrough infections and depended on the infecting variant of concern. While the delayed kinetics of immune recall provides a potential mechanism for the lack of early control of viral replication, the recall of antibodies coincided with viral clearance and likely underpins the protective effects of vaccination against severe COVID-19.

Original languageEnglish
Pages (from-to)1316-1326.e4
Number of pages16
JournalImmunity
Volume55
Issue number7
DOIs
Publication statusPublished - 12 Jul 2022

Keywords

  • B cell immunity
  • breakthrough infection
  • CD4 T cell immunity
  • CD8 T cell immunity
  • COVID-19 vaccines
  • Delta
  • neutralizing antibodies
  • Omicron
  • SARS-CoV-2
  • vaccination

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