Kathryn M Moore, Stephanie L Foster, Elizabeth J Elrod, Katharine A Floyd, M. Elliott Williams, Meenakshi Kar, Jacob Vander Velden, Madison Ellis, Ansa Malik, Bushra Wali, Stacey Lapp, Amanda Metz, Steven E Bosinger, Robert A Seder, Rama Rao Amara, Vineet D Menachery, Jacob E Kohlmeier, Arash Grakoui, Mehul S Suthar
{"title":"Eosinophils protect against SARS-CoV-2 following a vaccine breakthrough infection","authors":"Kathryn M Moore, Stephanie L Foster, Elizabeth J Elrod, Katharine A Floyd, M. Elliott Williams, Meenakshi Kar, Jacob Vander Velden, Madison Ellis, Ansa Malik, Bushra Wali, Stacey Lapp, Amanda Metz, Steven E Bosinger, Robert A Seder, Rama Rao Amara, Vineet D Menachery, Jacob E Kohlmeier, Arash Grakoui, Mehul S Suthar","doi":"10.1101/2024.08.08.607190","DOIUrl":null,"url":null,"abstract":"Waning immunity and the emergence of immune evasive SARS-CoV-2 variants jeopardize vaccine efficacy leading to breakthrough infections. We have previously shown that innate immune cells play a critical role in controlling SARS-CoV-2. To investigate the innate immune response during breakthrough infections, we modeled breakthrough infections by challenging low-dose vaccinated mice with a vaccine-mismatched SARS-CoV-2 Beta variant. We found that low-dose vaccinated infected mice had a 2-log reduction in lung viral burden, but increased immune cell infiltration in the lung parenchyma, characterized by monocytes, monocyte-derived macrophages, and eosinophils. Single cell RNA-seq revealed viral RNA was highly associated with eosinophils that corresponded to a unique IFN-γ biased signature. Antibody-mediated depletion of eosinophils in vaccinated mice resulted in increased virus replication and dissemination in the lungs, demonstrating that eosinophils in the lungs are protective during SARS-CoV-2 breakthrough infections. These results highlight the critical role for the innate immune response in vaccine mediated protection against SARS-CoV-2.","PeriodicalId":501182,"journal":{"name":"bioRxiv - Immunology","volume":"141 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"bioRxiv - Immunology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2024.08.08.607190","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Waning immunity and the emergence of immune evasive SARS-CoV-2 variants jeopardize vaccine efficacy leading to breakthrough infections. We have previously shown that innate immune cells play a critical role in controlling SARS-CoV-2. To investigate the innate immune response during breakthrough infections, we modeled breakthrough infections by challenging low-dose vaccinated mice with a vaccine-mismatched SARS-CoV-2 Beta variant. We found that low-dose vaccinated infected mice had a 2-log reduction in lung viral burden, but increased immune cell infiltration in the lung parenchyma, characterized by monocytes, monocyte-derived macrophages, and eosinophils. Single cell RNA-seq revealed viral RNA was highly associated with eosinophils that corresponded to a unique IFN-γ biased signature. Antibody-mediated depletion of eosinophils in vaccinated mice resulted in increased virus replication and dissemination in the lungs, demonstrating that eosinophils in the lungs are protective during SARS-CoV-2 breakthrough infections. These results highlight the critical role for the innate immune response in vaccine mediated protection against SARS-CoV-2.