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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Vaccines and Molecular Therapeutics

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1599408

Comparative single-cell immune responses in peripheral blood and lymph node of immunized SARS-CoV-2 challenged infant rhesus macaques

Provisionally accepted
Alexandra AnronikovAlexandra Anronikov1Cameron MeikleCameron Meikle2Emma Catherine MilliganEmma Catherine Milligan3Han ChenHan Chen1Nilanjan MukherjeeNilanjan Mukherjee1Zachary Bjornson-HooperZachary Bjornson-Hooper1Brice GaudilliereBrice Gaudilliere1Sizun JiangSizun Jiang4Sallie PermarSallie Permar5Koen Van RompayKoen Van Rompay6Garry NolanGarry Nolan1Kristina De ParisKristina De Paris3David Robert McIlwainDavid Robert McIlwain2*
  • 1Stanford University, Stanford, California, United States
  • 2University of Nevada, Reno, Reno, United States
  • 3University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • 4Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
  • 5Weill Cornell Medicine, Cornell University, New York, New York, United States
  • 6University of California, Davis, Davis, California, United States

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A better understanding of post-exposure immune responses in vaccinated individuals, particularly infants, is needed. Using a rhesus macaque model, we compared recipients of mRNA-or proteinbased SARS-CoV-2 vaccines administered in infancy with unvaccinated controls 7 days post-SARS-CoV-2 virus challenge. Mass cytometry profiling of peripheral blood mononuclear cells and dissociated mediastinal lymph node cells at 7 days post-challenge revealed tissue-specific differences between groups, representing a snapshot of immune activity at this point. Vaccinated animals showed lower frequencies of activated CD8+ T cells in blood and lower levels of monocyte and B cell subsets in lymph nodes, aligning with lower viral loads and milder pathology. Plasmacytoid dendritic cells-commonly depleted in circulation during severe human COVID-19-were preserved in the blood of vaccinated groups. Ex vivo stimulation demonstrated heightened inflammatory cell signaling from unvaccinated rhesus macaques, correlating with worse clinical outcomes. These findings enhance our understanding of a critical nonhuman primate model and underscore the utility of single-cell, tissue-level analyses in evaluating nextgeneration pediatric SARS-CoV-2 vaccine strategies.

Keywords: Vaccine, SARS-C0V-2, rhesus macaques, delta variant, Peripheral blood monocular cells, Lymph Node, COVID-19, cyTOF

Received: 24 Mar 2025; Accepted: 22 Aug 2025.

Copyright: © 2025 Anronikov, Meikle, Milligan, Chen, Mukherjee, Bjornson-Hooper, Gaudilliere, Jiang, Permar, Van Rompay, Nolan, De Paris and McIlwain. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: David Robert McIlwain, University of Nevada, Reno, Reno, United States

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material