嗜酸性粒细胞可在疫苗突破性感染后抵御 SARS-CoV-2

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
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摘要

免疫力的下降和免疫逃避型 SARS-CoV-2 变异株的出现会危及疫苗的效果,从而导致突破性感染。我们以前的研究表明,先天性免疫细胞在控制 SARS-CoV-2 方面发挥着关键作用。为了研究突破性感染期间的先天性免疫反应,我们用疫苗不匹配的 SARS-CoV-2 Beta 变异株挑战低剂量接种疫苗的小鼠,从而模拟突破性感染。我们发现,接种低剂量疫苗的受感染小鼠肺部病毒负荷减少了 2 个对数,但肺实质中的免疫细胞浸润却增加了,其特征是单核细胞、单核细胞衍生巨噬细胞和嗜酸性粒细胞。单细胞RNA-seq显示病毒RNA与嗜酸性粒细胞高度相关,与独特的IFN-γ偏倚特征相对应。抗体介导的疫苗接种小鼠嗜酸性粒细胞耗竭会导致病毒在肺部的复制和传播增加,这表明在 SARS-CoV-2 突破性感染期间,肺部的嗜酸性粒细胞具有保护作用。这些结果凸显了先天性免疫反应在疫苗介导的 SARS-CoV-2 保护中的关键作用。
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Eosinophils protect against SARS-CoV-2 following a vaccine breakthrough infection
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.
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