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Prior SARS-Cov-2 infection affects adaptive immune responses to Omicron BA.4/BA.5 mRNA booster

  1. Author:
    Wachter, Brianna T
    Xu, Qin
    Shi, Lihong
    Burbelo, Peter D
    Myint-Hpu, Kathy
    Schwartzberg, Pamela L
    Rehman,Tauseef
    Dewar,Robin
    Boswell, Kristin L
    Koup, Richard A
    Oguz, Cihan
    Imberti, Luisa
    Bellusci, Lorenza
    Pourhashemi, Sara
    Khurana, Surender
    Manthiram, Kalpana
    Notarangelo, Luigi D
    Delmonte, Ottavia M

  2. Author Address

    Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, USA., Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD, USA., Adeno-Associated Virus Biology Section, NIDCR, NIH, Bethesda, MD, USA., Virus Isolation and Serology Laboratory, Frederick National Laboratory, Frederick, MD, USA., Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, MD, USA., Integrated Data Sciences Section, Research Technologies Branch, NIAID, NIH, Bethesda, MD, USA., Spedali Civili di Brescia, Universita 39; degli studi di Brescia, Italy., Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, MD., Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, USA. Electronic address: luigi.notarangelo2@nih.gov., Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, USA. Electronic address: ottavia.delmonte@nih.gov.,
    1. Year: 2025
    2. Date: Mar 03
    3. Epub Date: 2025 03 03
  2. Journal: The journal of Allergy and Clinical Immunology.
  4. Type of Article: Article
  1. Abstract:

    Bivalent COVID-19 mRNA vaccines encoding Wuhan-1 and Omicron BA.4/5 spike proteins can prevent SARS-CoV-2 infection, but the quality of adaptive immune responses and the importance of hybrid immunity are not well-documented. Adaptive immune responses to the bivalent vaccine were studied in 40 healthy participants with (COVID+) or without (COVID-) prior history of SARS-CoV-2 infection. We analyzed anti-N and anti-S IgG titers and surrogate virus neutralization capacity against variants of concern (VOCs) and assessed SARS-CoV-2 specific B and T cell responses by high-dimensional spectral flow cytometry, intracellular cytokine staining assay upon stimulation with SARS-CoV-2 peptides and TRB and IGH repertoire analysis. The COVID+ group had higher anti-S IgG levels pre- and post-booster and higher neutralization activity against BA.4/5 than the COVID- group. Spike antibody levels positively correlated with neutralizing activity against Omicron VOCs in all participants. For VOCs, lowest neutralization capacity was against XBB1.5. At baseline, the proportion of S1+ RBD+ B cells was higher in COVID+ than in COVID- subjects, but an increase of these cells post-boost was detected only in the COVID- group. Consistent with natural infection, COVID+ subjects had a higher frequency of IgA+ CXCR3+S1+RBD+ B cells at baseline than COVID- subjects. CD4+ memory T cells responses and breath of class II epitope SARS-CoV-2 specific clonotypes were increased post-boost only in COVID- participants. The bivalent vaccine induces robust adaptive immune responses against the Omicron variant. Prior SARS-CoV-2 infection provides increased protection, but optimal timing of booster administration after natural infection should be defined to maximize benefits. Copyright © 2025. Published by Elsevier Inc.

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External Sources

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  2. DOI: 10.1016/j.jaci.2025.02.026
  3. PMID: 40044048
  4. PII : S0091-6749(25)00256-8

Library Notes

  1. Fiscal Year: FY2024-2025
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