Binding and Avidity Signatures of Polyclonal Sera From Individuals With Different Exposure Histories to Severe Acute Respiratory Syndrome Coronavirus 2 Infection, Vaccination, and Omicron Breakthrough Infections

Gagandeep Singh, Anass Abbad, Johnstone Tcheou, Demodara Rao Mendu, Adolfo Firpo-Betancourt, Charles Gleason, Komal Srivastava, Carlos Cordon-Cardo, Viviana Simon, Florian Krammer, Juan Manuel Carreño

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: The number of exposures to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to vaccine antigens affect the magnitude and avidity of the polyclonal response. Methods: We studied binding and avidity of different antibody isotypes to the spike, the receptor-binding domain (RBD), and the nucleoprotein (NP) of wild-type (WT) and BA.1 SARS-CoV-2 in convalescent, mRNA vaccinated and/or boosted, hybrid immune individuals and in individuals with breakthrough cases during the peak of the BA.1 wave. Results: We found an increase in spike-binding antibodies and antibody avidity with increasing number of exposures to infection and/or vaccination. NP antibodies were detectible in convalescent individuals and a proportion of breakthrough cases, but they displayed low avidity. Omicron breakthrough infections elicited high levels of cross-reactive antibodies between WT and BA.1 antigens in vaccinated individuals without prior infection directed against the spike and RBD. The magnitude of the antibody response and avidity correlated with neutralizing activity against WT virus. Conclusions: The magnitude and quality of the antibody response increased with the number of antigenic exposures, including breakthrough infections. However, cross-reactivity of the antibody response after BA.1 breakthroughs, was affected by the number of prior exposures.

Original languageEnglish
Pages (from-to)564-575
Number of pages12
JournalJournal of Infectious Diseases
Volume228
Issue number5
DOIs
StatePublished - 1 Sep 2023

Keywords

  • SARS-CoV-2
  • antibodies
  • avidity
  • neutralization
  • omicron

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