SARS-CoV-2 booster vaccination rescues attenuated IgG1 memory B cell response in primary antibody deficiency patients

Frank J. Lin, Alexa Michelle Altman Doss, Hannah G. Davis-Adams, Lucas J. Adams, Christopher H. Hanson, Laura A. VanBlargan, Chieh Yu Liang, Rita E. Chen, Jennifer Marie Monroy, H. James Wedner, Anthony Kulczycki, Tarisa L. Mantia, Caitlin C. O’Shaughnessy, Saravanan Raju, Fang R. Zhao, Elise Rizzi, Christopher J. Rigell, Tiffany Biason Dy, Andrew L. Kau, Zhen RenJackson S. Turner, Jane A. O’Halloran, Rachel M. Presti, Daved H. Fremont, Peggy L. Kendall, Ali H. Ellebedy, Philip A. Mudd, Michael S. Diamond, Ofer Zimmerman, Brian J. Laidlaw

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Although SARS-CoV-2 vaccines have proven effective in eliciting a protective immune response in healthy individuals, their ability to induce a durable immune response in immunocompromised individuals remains poorly understood. Primary antibody deficiency (PAD) syndromes are among the most common primary immunodeficiency disorders in adults and are characterized by hypogammaglobulinemia and impaired ability to mount robust antibody responses following infection or vaccination. Methods: Here, we present an analysis of both the B and T cell response in a prospective cohort of 30 individuals with PAD up to 150 days following initial COVID-19 vaccination and 150 days post mRNA booster vaccination. Results: After the primary vaccination series, many of the individuals with PAD syndromes mounted SARS-CoV-2 specific memory B and CD4+ T cell responses that overall were comparable to healthy individuals. Nonetheless, individuals with PAD syndromes had reduced IgG1+ and CD11c+ memory B cell responses following the primary vaccination series, with the defect in IgG1 class-switching rescued following mRNA booster doses. Boosting also elicited an increase in the SARS-CoV-2-specific B and T cell response and the development of Omicron-specific memory B cells in COVID-19-naïve PAD patients. Individuals that lacked detectable B cell responses following primary vaccination did not benefit from booster vaccination. Conclusion: Together, these data indicate that SARS-CoV-2 vaccines elicit memory B and T cells in most PAD patients and highlights the importance of booster vaccination in immunodeficient individuals.

Original languageEnglish
Article number1033770
JournalFrontiers in immunology
Volume13
DOIs
StatePublished - Dec 22 2022

Keywords

  • B cells
  • SARS-CoV-2
  • common variable immunodeficiency
  • hypogammaglobulinemia
  • immune memory
  • primary antibody deficiency
  • specific antibody deficiency
  • vaccination

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