mRNA vaccine boosting enhances antibody responses against SARS-CoV-2 Omicron variant in individuals with antibody deficiency syndromes

Ofer Zimmerman, Alexa Michelle Altman Doss, Paulina Kaplonek, Chieh Yu Liang, Laura A. VanBlargan, Rita E. Chen, Jennifer Marie Monroy, H. James Wedner, Anthony Kulczycki, Tarisa L. Mantia, Caitlin C. O'Shaughnessy, Hannah G. Davis-Adams, Harry L. Bertera, Lucas J. Adams, Saravanan Raju, Fang R. Zhao, 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, Galit Alter, Michael S. Diamond

Research output: Contribution to journalArticlepeer-review

Abstract

Individuals with primary antibody deficiency (PAD) syndromes have poor humoral immune responses requiring immunoglobulin replacement therapy. We followed individuals with PAD after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination by evaluating their immunoglobulin replacement products and serum for anti-spike binding, Fcγ receptor (FcγR) binding, and neutralizing activities. The immunoglobulin replacement products tested have low anti-spike and receptor-binding domain (RBD) titers and neutralizing activity. In coronavirus disease 2019 (COVID-19)-naive individuals with PAD, anti-spike and RBD titers increase after mRNA vaccination but wane by 90 days. Those vaccinated after SARS-CoV-2 infection develop higher and more sustained responses comparable with healthy donors. Most vaccinated individuals with PAD have serum-neutralizing antibody titers above an estimated correlate of protection against ancestral SARS-CoV-2 and Delta virus but not against Omicron virus, although this is improved by boosting. Thus, some immunoglobulin replacement products likely have limited protective activity, and immunization and boosting of individuals with PAD with mRNA vaccines should confer at least short-term immunity against SARS-CoV-2 variants, including Omicron.

Original languageEnglish
Article number100653
JournalCell Reports Medicine
Volume3
Issue number6
DOIs
StatePublished - Jun 21 2022

Keywords

  • COVID-19
  • SARS-CoV-2
  • combined variable antibody deficiency
  • hypogammaglobulinemia
  • immune response
  • mRNA vaccine
  • neutralization
  • specific antibody deficiency
  • vaccine

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