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

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

Abstract

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 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.

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.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 next-generation pediatric SARS-CoV-2 vaccine strategies.