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 journalArticlepeer-review


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 languageEnglish
Pages (from-to)6037-6051.e14
Issue number25
StatePublished - 9 Dec 2021

Bibliographical note

Publisher Copyright:
© 2021 Elsevier Inc.


  • 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


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