{"doi":"10.1371/journal.ppat.1013752","title":"Monocyte-eosinophil signaling axis promotes vaccine-mediated protection against SARS-CoV-2","abstract":"COVID-19 vaccines provide robust protection against severe disease, hospitalization, and death. Neutralizing antibodies are a strong correlate of protection and can prevent SARS-CoV-2 infection of the lungs. We used a conventional laboratory mouse model combined with high- or low-dose vaccination to understand the early immunological response following SARS-CoV-2 infection in the lungs of vaccinated mice. The lungs of high-dose vaccinated mice were completely protected against SARS-CoV-2 infection whereas low-dose vaccinated mice were partially protected. We observed a greater influx of total monocytes, macrophages, dendritic cells, neutrophils, and eosinophils in the lungs of low-dose vaccinated mice compared to naïve infected mice. The different proportions of innate immune cells in the lungs indicated that infection in low-dose vaccinated mice induces a unique inflammatory environment compared to naïve infected or uninfected mice. A prominent feature of infection of low-dose vaccinated mice was infiltration of eosinophils in the lungs, which we observed across different COVID-19 vaccines and SARS-CoV-2 variants. Single cell transcriptional profiling of lung parenchymal immune cells showed that viral RNA was predominantly associated with eosinophils. Eosinophils from low-dose vaccinated mice were transcriptionally distinct from naïve mice after challenge and showed an IFN-γ biased signature. Further, monocytes from low-dose vaccinated mice expressed eotaxin-2, suggesting a monocyte-eosinophil signaling axis. Antibody mediated depletion of eosinophils in low-dose vaccinated mice resulted in increased virus replication and dissemination in the lungs. These findings demonstrate the protective nature of eosinophils during SARS-CoV-2 infection in the context of vaccination and highlight quantitative and qualitative differences in the immune response in a model for vaccine breakthrough infection.","journal":"PLoS Pathogens","year":2025,"id":535646,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":242848,"name":"Stephanie L. 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