AUTHOR=Anronikov Sasha , Meikle Cameron , Milligan Emma C. , Chen Han , Mukherjee Nilanjan , Bjornson Zach , Gaudillière Brice , Jiang Sizun , Permar Sallie R. , Van Rompay Koen K. A. , Nolan Garry P. , De Paris Kristina , McIlwain David R. 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1599408

DOI=10.3389/fimmu.2025.1599408

ISSN=1664-3224

ABSTRACT=IntroductionA better understanding of post-exposure immune responses in vaccinated individuals, particularly infants, is needed.MethodsUsing a rhesus macaque model, we compared recipients of mRNA- or protein-based 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.ResultsVaccinated 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.DiscussionThese findings enhance our understanding of a critical nonhuman primate model and underscore the utility of single-cell, tissue-level analyses in evaluating next-generation pediatric SARS-CoV-2 vaccine strategies.