A defective viral genome strategy elicits broad protective immunity against respiratory viruses

Yinghong Xiao; Peter V. Lidsky; Yuta Shirogane; Ranen Aviner; Chien-Ting Wu; Weiyi Li; Weihao Zheng; Dale Talbot; Adam Catching; Gilad Doitsh; Weiheng Su; Colby E. Gekko; Arabinda Nayak; Joel D. Ernst; Leonid Brodsky; Elia Brodsky; Elsa Rousseau; Sara Capponi; Simone Bianco; Robert Nakamura; Peter K. Jackson; Judith Frydman; Raul Andino

doi:10.1016/j.cell.2021.11.023

A defective viral genome strategy elicits broad protective immunity against respiratory viruses

Yinghong Xiao, Peter V. Lidsky, Yuta Shirogane, Ranen Aviner, Chien-Ting Wu, Weiyi Li, Weihao Zheng, Dale Talbot, Adam Catching, Gilad Doitsh, Weiheng Su, Colby E. Gekko, Arabinda Nayak, Joel D. Ernst, Leonid Brodsky, Elia Brodsky, Elsa Rousseau, Sara Capponi, Simone Bianco, Robert NakamuraPeter K. Jackson, Judith Frydman, Raul Andino^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

51 Citations (Scopus)

Abstract

RNA viruses generate defective viral genomes (DVGs) that can interfere with replication of the parental wild-type virus. To examine their therapeutic potential, we created a DVG by deleting the capsid-coding region of poliovirus. Strikingly, intraperitoneal or intranasal administration of this genome, which we termed eTIP1, elicits an antiviral response, inhibits replication, and protects mice from several RNA viruses, including enteroviruses, influenza, and SARS-CoV-2. While eTIP1 replication following intranasal administration is limited to the nasal cavity, its antiviral action extends non-cell-autonomously to the lungs. eTIP1 broad-spectrum antiviral effects are mediated by both local and distal type I interferon responses. Importantly, while a single eTIP1 dose protects animals from SARS-CoV-2 infection, it also stimulates production of SARS-CoV-2 neutralizing antibodies that afford long-lasting protection from SARS-CoV-2 reinfection. Thus, eTIP1 is a safe and effective broad-spectrum antiviral generating short- and long-term protection against SARS-CoV-2 and other respiratory infections in animal models. © 2021 Elsevier Inc.

Original language	English
Pages (from-to)	6037-6051.e14
Journal	Cell
Volume	184
Issue number	25
Online published	18 Nov 2021
DOIs	https://doi.org/10.1016/j.cell.2021.11.023
Publication status	Published - 9 Dec 2021
Externally published	Yes

Research Keywords

antiviral
broad-spectrum
defective viral genomes
innate immunity
interferon
respiratory infection
RNA viruses
SARS-CoV-2

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Xiao, Y., Lidsky, P. V., Shirogane, Y., Aviner, R., Wu, C.-T., Li, W., Zheng, W., Talbot, D., Catching, A., Doitsh, G., Su, W., Gekko, C. E., Nayak, A., Ernst, J. D., Brodsky, L., Brodsky, E., Rousseau, E., Capponi, S., Bianco, S., ... Andino, R. (2021). A defective viral genome strategy elicits broad protective immunity against respiratory viruses. Cell, 184(25), 6037-6051.e14. https://doi.org/10.1016/j.cell.2021.11.023

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title = "A defective viral genome strategy elicits broad protective immunity against respiratory viruses",

abstract = "RNA viruses generate defective viral genomes (DVGs) that can interfere with replication of the parental wild-type virus. To examine their therapeutic potential, we created a DVG by deleting the capsid-coding region of poliovirus. Strikingly, intraperitoneal or intranasal administration of this genome, which we termed eTIP1, elicits an antiviral response, inhibits replication, and protects mice from several RNA viruses, including enteroviruses, influenza, and SARS-CoV-2. While eTIP1 replication following intranasal administration is limited to the nasal cavity, its antiviral action extends non-cell-autonomously to the lungs. eTIP1 broad-spectrum antiviral effects are mediated by both local and distal type I interferon responses. Importantly, while a single eTIP1 dose protects animals from SARS-CoV-2 infection, it also stimulates production of SARS-CoV-2 neutralizing antibodies that afford long-lasting protection from SARS-CoV-2 reinfection. Thus, eTIP1 is a safe and effective broad-spectrum antiviral generating short- and long-term protection against SARS-CoV-2 and other respiratory infections in animal models. {\textcopyright} 2021 Elsevier Inc.",

keywords = "antiviral, broad-spectrum, defective viral genomes, innate immunity, interferon, respiratory infection, RNA viruses, SARS-CoV-2",

author = "Yinghong Xiao and Lidsky, {Peter V.} and Yuta Shirogane and Ranen Aviner and Chien-Ting Wu and Weiyi Li and Weihao Zheng and Dale Talbot and Adam Catching and Gilad Doitsh and Weiheng Su and Gekko, {Colby E.} and Arabinda Nayak and Ernst, {Joel D.} and Leonid Brodsky and Elia Brodsky and Elsa Rousseau and Sara Capponi and Simone Bianco and Robert Nakamura and Jackson, {Peter K.} and Judith Frydman and Raul Andino",

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month = dec,

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doi = "10.1016/j.cell.2021.11.023",

language = "English",

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Xiao, Y, Lidsky, PV, Shirogane, Y, Aviner, R, Wu, C-T, Li, W, Zheng, W, Talbot, D, Catching, A, Doitsh, G, Su, W, Gekko, CE, Nayak, A, Ernst, JD, Brodsky, L, Brodsky, E, Rousseau, E, Capponi, S, Bianco, S, Nakamura, R, Jackson, PK, Frydman, J & Andino, R 2021, 'A defective viral genome strategy elicits broad protective immunity against respiratory viruses', Cell, vol. 184, no. 25, pp. 6037-6051.e14. https://doi.org/10.1016/j.cell.2021.11.023

TY - JOUR

T1 - A defective viral genome strategy elicits broad protective immunity against respiratory viruses

AU - Xiao, Yinghong

AU - Lidsky, Peter V.

AU - Shirogane, Yuta

AU - Aviner, Ranen

AU - Wu, Chien-Ting

AU - Li, Weiyi

AU - Zheng, Weihao

AU - Talbot, Dale

AU - Catching, Adam

AU - Doitsh, Gilad

AU - Su, Weiheng

AU - Gekko, Colby E.

AU - Nayak, Arabinda

AU - Ernst, Joel D.

AU - Brodsky, Leonid

AU - Brodsky, Elia

AU - Rousseau, Elsa

AU - Capponi, Sara

AU - Bianco, Simone

AU - Nakamura, Robert

AU - Jackson, Peter K.

AU - Frydman, Judith

AU - Andino, Raul

PY - 2021/12/9

Y1 - 2021/12/9

N2 - RNA viruses generate defective viral genomes (DVGs) that can interfere with replication of the parental wild-type virus. To examine their therapeutic potential, we created a DVG by deleting the capsid-coding region of poliovirus. Strikingly, intraperitoneal or intranasal administration of this genome, which we termed eTIP1, elicits an antiviral response, inhibits replication, and protects mice from several RNA viruses, including enteroviruses, influenza, and SARS-CoV-2. While eTIP1 replication following intranasal administration is limited to the nasal cavity, its antiviral action extends non-cell-autonomously to the lungs. eTIP1 broad-spectrum antiviral effects are mediated by both local and distal type I interferon responses. Importantly, while a single eTIP1 dose protects animals from SARS-CoV-2 infection, it also stimulates production of SARS-CoV-2 neutralizing antibodies that afford long-lasting protection from SARS-CoV-2 reinfection. Thus, eTIP1 is a safe and effective broad-spectrum antiviral generating short- and long-term protection against SARS-CoV-2 and other respiratory infections in animal models. © 2021 Elsevier Inc.

AB - RNA viruses generate defective viral genomes (DVGs) that can interfere with replication of the parental wild-type virus. To examine their therapeutic potential, we created a DVG by deleting the capsid-coding region of poliovirus. Strikingly, intraperitoneal or intranasal administration of this genome, which we termed eTIP1, elicits an antiviral response, inhibits replication, and protects mice from several RNA viruses, including enteroviruses, influenza, and SARS-CoV-2. While eTIP1 replication following intranasal administration is limited to the nasal cavity, its antiviral action extends non-cell-autonomously to the lungs. eTIP1 broad-spectrum antiviral effects are mediated by both local and distal type I interferon responses. Importantly, while a single eTIP1 dose protects animals from SARS-CoV-2 infection, it also stimulates production of SARS-CoV-2 neutralizing antibodies that afford long-lasting protection from SARS-CoV-2 reinfection. Thus, eTIP1 is a safe and effective broad-spectrum antiviral generating short- and long-term protection against SARS-CoV-2 and other respiratory infections in animal models. © 2021 Elsevier Inc.

KW - antiviral

KW - broad-spectrum

KW - defective viral genomes

KW - innate immunity

KW - interferon

KW - respiratory infection

KW - RNA viruses

KW - SARS-CoV-2

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UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85120620149&origin=recordpage

U2 - 10.1016/j.cell.2021.11.023

DO - 10.1016/j.cell.2021.11.023

M3 - RGC 21 - Publication in refereed journal

C2 - 34852237

SN - 0092-8674

VL - 184

SP - 6037-6051.e14

JO - Cell

JF - Cell

IS - 25

ER -

A defective viral genome strategy elicits broad protective immunity against respiratory viruses

Abstract

Research Keywords

UN SDGs

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