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

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

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.

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

Keywords

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

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/j.cell.2021.11.023

Cite this

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

Xiao, Y, Lidsky, PV, Shirogane, Y, Aviner, R, Wu, CT, 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

@article{66bb603820854c3686ebfdc6a0f0798d,

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.",

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

author = "Yinghong Xiao and Lidsky, {Peter V.} and Yuta Shirogane and Ranen Aviner and Wu, {Chien Ting} 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",

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2021",

month = dec,

day = "9",

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

language = "English (US)",

volume = "184",

pages = "6037--6051.e14",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "25",

}

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.

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.

KW - RNA viruses

KW - SARS-CoV-2

KW - antiviral

KW - broad-spectrum

KW - defective viral genomes

KW - innate immunity

KW - interferon

KW - respiratory infection

UR - http://www.scopus.com/inward/record.url?scp=85120620149&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85120620149&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2021.11.023

DO - 10.1016/j.cell.2021.11.023

M3 - Article

C2 - 34852237

AN - SCOPUS:85120620149

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

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this