Evidence map›Paper›PMID 40817105›Full record

ArticleNature communications2025

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

Sheetal Trivedi, Piyush Dravid, Tim C Passchier, Satyapramod Murthy, Kripa Shanker Kasudhan, Narendran Reguraman, Justin Kellar, Rahul Chandra, Cole Cassady, Peter D Burbelo and 4 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Sheetal Trivedi *Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
Piyush Dravid *Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
Tim C PasschierNuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-1306-5853
Satyapramod MurthyCenter for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
Kripa Shanker KasudhanCenter for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
Narendran ReguramanCenter for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
Justin KellarCenter for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
Rahul ChandraCenter for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
Cole CassadyCenter for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
Peter D BurbeloAdeno-Associated Virus Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-1717-048X
Arash GrakouiEmory National Primate Research Center, Emory University, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-6002-7518
Himanshu SharmaCenter for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
Peter SimmondsNuffield Department of Medicine, University of Oxford, Oxford, UK.
Amit KapoorCenter for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA. amit.kapoor@nationwidechildrens.org.ORCID http://orcid.org/0000-0002-8117-7347

Funding

Immune correlates of protection against hepacivirus persistence.R01AI151175 · NIAID · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI KAPOOR, AMIT · 2021 to 2024
$2.5M
Animal Model to study heterogeneous outcomes of HCV Infection and PathogenesisR01AI183877 · NIAID · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI Amit Kapoor · 2024 to 2026
$2.4M
Viral Determinants of Chronic Hepacivirus InfectionR01AI185926 · NIAID · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI Amit Kapoor · 2024 to 2026
$2.0M
A sequence-independent approach for attenuating hepacivirusesR21AI171928 · NIAID · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI KAPOOR, AMIT · 2023 to 2024
$429k
NIAID NIH HHS R01 AI151175NIAID NIH HHS R01 AI183877NIAID NIH HHS R01 AI185926NIAID NIH HHS R21 AI171928U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) AI171928, AI151175, AI185926, AI183877
6 · The paper itself

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.

Indexed as

HepacivirusHepatitis C, ChronicViral Hepatitis VaccinesAnimalsDisease Models, AnimalMaleNanoparticlesRatsRNA, ViralT-LymphocytesVaccinationVaccines, AttenuatedRNA, ViralVaccines, AttenuatedViral Hepatitis Vaccines

Identifiers

PMID40817105
PMCPMC12356917

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.