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Cell
. 2021 Nov 18;S0092-8674(21)01338-6.
doi: 10.1016/j.cell.2021.11.023. Online ahead of print.
A defective viral genome strategy elicits broad protective immunity against respiratory viruses
Yinghong Xiao 1 , Peter V Lidsky 1 , Yuta Shirogane 2 , Ranen Aviner 3 , Chien-Ting Wu 4 , Weiyi Li 1 , Weihao Zheng 5 , Dale Talbot 6 , Adam Catching 1 , Gilad Doitsh 1 , Weiheng Su 7 , Colby E Gekko 1 , Arabinda Nayak 3 , Joel D Ernst 5 , Leonid Brodsky 8 , Elia Brodsky 9 , Elsa Rousseau 10 , Sara Capponi 10 , Simone Bianco 10 , Robert Nakamura 11 , Peter K Jackson 4 , Judith Frydman 12 , Raul Andino 13
Affiliations
- PMID: 34852237
- PMCID: PMC8598942
- DOI: 10.1016/j.cell.2021.11.023
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.