IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-62813-8.html
   My bibliography  Save this article

Design and nonviral delivery of live attenuated vaccine to prevent chronic hepatitis C virus-like infection

Author

Listed:
  • Sheetal Trivedi

    (The Research Institute at Nationwide Children’s Hospital)

  • Piyush Dravid

    (The Research Institute at Nationwide Children’s Hospital)

  • Tim C. Passchier

    (University of Oxford)

  • Satyapramod Murthy

    (The Research Institute at Nationwide Children’s Hospital)

  • Kripa Shanker Kasudhan

    (The Research Institute at Nationwide Children’s Hospital)

  • Narendran Reguraman

    (The Research Institute at Nationwide Children’s Hospital)

  • Justin Kellar

    (The Research Institute at Nationwide Children’s Hospital)

  • Rahul Chandra

    (The Research Institute at Nationwide Children’s Hospital)

  • Cole Cassady

    (The Research Institute at Nationwide Children’s Hospital)

  • Peter D. Burbelo

    (National Institutes of Health)

  • Arash Grakoui

    (Emory University
    Emory University School of Medicine)

  • Himanshu Sharma

    (The Research Institute at Nationwide Children’s Hospital)

  • Peter Simmonds

    (University of Oxford)

  • Amit Kapoor

    (The Research Institute at Nationwide Children’s Hospital
    The Ohio State University)

Abstract

An effective vaccine for the hepatitis C virus (HCV) remains an unmet medical need. There is no animal model for assessing HCV vaccines; however, rodent hepacivirus (RHV) infection in laboratory rats recapitulates the lifelong chronic hepatotropic infection and immune evasion of HCV. Here, we designed a live-attenuated vaccine (LAV) for RHV and determined its immunogenicity and efficacy for preventing chronic infection. The LAV strains are generated by synonymous mutagenesis to increase the frequencies of naturally suppressed dinucleotides, UpA or CpG, in genomic regions that lack extensive RNA secondary structures. Rats vaccinated using LAV containing infectious virions (LAV-IV), or lipid nanoparticle-encapsulated viral RNA (LNP-vRNA) developed short-term viremia and robust T cell responses. After challenge with RHV-rn1, while all unvaccinated rats developed chronic infection, 75% and 85% of rats vaccinated with LAV-IV and LAV-vRNA cleared the infection. Clearance of RHV-rn1 was associated with expansion of memory T cells, transient rise in serum ALT, and, more importantly, enhanced protection against reinfection. In conclusion, we identified a genomic region of hepacivirus that can be synonymously mutated to attenuate its persistence, and vaccines based on these modified genomes protect against chronic hepacivirus infection, a strategy with an apparent translational path toward HCV immunization.

Suggested Citation

  • Sheetal Trivedi & Piyush Dravid & Tim C. Passchier & Satyapramod Murthy & Kripa Shanker Kasudhan & Narendran Reguraman & Justin Kellar & Rahul Chandra & Cole Cassady & Peter D. Burbelo & Arash Grakoui, 2025. "Design and nonviral delivery of live attenuated vaccine to prevent chronic hepatitis C virus-like infection," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62813-8
    DOI: 10.1038/s41467-025-62813-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-62813-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-62813-8?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Alex S. Hartlage & Satyapramod Murthy & Arvind Kumar & Sheetal Trivedi & Piyush Dravid & Himanshu Sharma & Christopher M. Walker & Amit Kapoor, 2019. "Vaccination to prevent T cell subversion can protect against persistent hepacivirus infection," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    2. David G. Bowen & Christopher M. Walker, 2005. "Adaptive immune responses in acute and chronic hepatitis C virus infection," Nature, Nature, vol. 436(7053), pages 946-952, August.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Anne Burgevin & Loredana Saveanu & Yohan Kim & Émilie Barilleau & Maya Kotturi & Alessandro Sette & Peter van Endert & Bjoern Peters, 2008. "A Detailed Analysis of the Murine TAP Transporter Substrate Specificity," PLOS ONE, Public Library of Science, vol. 3(6), pages 1-8, June.
    2. Kieran English & Rain Kwan & Lauren E. Holz & Claire McGuffog & Jelte M. M. Krol & Daryan Kempe & Tsuneyasu Kaisho & William R. Heath & Leszek Lisowski & Maté Biro & Geoffrey W. McCaughan & David G. B, 2024. "A hepatic network of dendritic cells mediates CD4 T cell help outside lymphoid organs," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62813-8. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.