Human T cells efficiently control RSV infection

• Type of Material: Article
• Authors: Chandrav De, University of North Carolina (UNC) at Chapel Hill; Raymond J Pickles, University of North Carolina (UNC) at Chapel Hill; Wenbo Yao, University of North Carolina (UNC) at Chapel Hill; Baolin Liao, University of North Carolina (UNC) at Chapel Hill; Allison Boone, University of North Carolina (UNC) at Chapel Hill; Mingyu Choi, University of North Carolina (UNC) at Chapel Hill; Diana M Battaglia, University of North Carolina (UNC) at Chapel Hill; Frederic B Askin, University of North Carolina (UNC) at Chapel Hill; Jason K Whitmire, University of North Carolina (UNC) at Chapel Hill; Guido Silvestri, Emory University; J. Victor Garcia, University of North Carolina (UNC) at Chapel Hill; Angela Wahl, University of North Carolina (UNC) at Chapel Hill
• Language: English
• Date: 2023-06-08
• Publisher: AMER SOC CLINICAL INVESTIGATION INC
• Publication Version: Final Published Version
• Copyright Statement: © 2023, De et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1172/jci.insight.168110
• Title of Journal or Parent Work: JCI INSIGHT
• Volume: 8
• Issue: 11
• Grant/Funding Information: This work was funded in part by NIH grants R21AI113736 (RJP), R01AI123010 (AW), R01AI111899 (JVG), R01AI140799 (JVG), and R01MH108179 (JVG).
• Keywords: RESPIRATORY SYNCYTIAL VIRUS; CLEAR VIRUS; Research & Experimental Medicine; IMPACT; TARGET; MEMORY; DISEASE; Life Sciences & Biomedicine; IMMUNITY; Medicine, Research & Experimental; Science & Technology
• Research Categories: Biology, Genetics; Biology, Microbiology; Health Sciences, Pathology; Health Sciences, Immunology

Abstract

Respiratory syncytial virus (RSV) infection causes significant morbidity and mortality in infants, immunocompromised individuals, and older individuals. There is an urgent need for effective antivirals and vaccines for high-risk individuals. We used 2 complementary in vivo models to analyze RSV-associated human lung pathology and human immune correlates of protection. RSV infection resulted in widespread human lung epithelial damage, a proinflammatory innate immune response, and elicited a natural adaptive human immune response that conferred protective immunity. We demonstrated a key role for human T cells in controlling RSV infection. Specifically, primed human CD8+ T cells or CD4+ T cells effectively and independently control RSV replication in human lung tissue in the absence of an RSV-specific antibody response. These preclinical data support the development of RSV vaccines, which also elicit effective T cell responses to improve RSV vaccine efficacy.