Fc-fused IL-7 provides broad antiviral effects against respiratory virus infections through IL-17A-producing pulmonary innate-like T cells
Dong-il Kwon, Subin Park, Yu‐Jin Jeong, Young‐Min Kim, Jeongyong Min, Changhyung Lee, Jung-ah Choi, Yoon Ha Choi, Hyun-Jung Kong, Youngwon Choi, Seungtae Baek, Kun-Joo Lee, Yeon‐Woo Kang, Chaerim Jeong, Gihoon You, Youngsik Oh, Sun‐Kyoung Im, Manki Song, Jong Kim, Jun Chang, Donghoon Choi, Seung‐Woo Lee
Abstract
Repeated pandemics caused by the influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV) have resulted in serious problems in global public health, emphasizing the need for broad-spectrum antiviral therapeutics against respiratory virus infections. Here, we show the protective effects of long-acting recombinant human interleukin-7 fused with hybrid Fc (rhIL-7-hyFc) against major respiratory viruses, including influenza virus, SARS-CoV-2, and respiratory syncytial virus. Administration of rhIL-7-hyFc in a therapeutic or prophylactic regimen induces substantial antiviral effects. During an influenza A virus (IAV) infection, rhIL-7-hyFc treatment increases pulmonary T cells composed of blood-derived interferon γ (IFNγ)+ conventional T cells and locally expanded IL-17A+ innate-like T cells. Single-cell RNA transcriptomics reveals that rhIL-7-hyFc upregulates antiviral genes in pulmonary T cells and induces clonal expansion of type 17 innate-like T cells. rhIL-7-hyFc-mediated disease prevention is dependent on IL-17A in both IAV- and SARS-CoV-2-infected mice. Collectively, we suggest that rhIL-7-hyFc can be used as a broadly active therapeutic for future respiratory virus pandemic.