Evidence map›Paper›PMID 33992803›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021

Lipid-nanoparticle-encapsulated mRNA vaccines induce protective memory CD8 T cells against a lethal viral infection.

Cory J Knudson, Pedro Alves-Peixoto, Hiromi Muramatsu, Colby Stotesbury, Lingjuan Tang, Paulo J C Lin, Ying K Tam, Drew Weissman, Norbert Pardi, Luis J Sigal

Open access · greenAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 10% of its field
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

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. AnScience immunology · 2025
    Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. The roles of CD4Molecular therapy. Nucleic acids · 2024
    Article
  18. mRNA-LNP vaccine-induced CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  19. Pseudouridine andRSC chemical biology · 2024
    Review
  20. 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

10 authors at 4 institutions in 3 countries.

Cory J KnudsonDepartment of Microbiology and Immunology, Bluemle Life Science Building, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Pedro Alves-PeixotoDepartment of Microbiology and Immunology, Bluemle Life Science Building, Thomas Jefferson University, Philadelphia, PA 19107, USA; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga 4710-057, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães 4806-909, Portugal.
Hiromi MuramatsuDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Colby StotesburyDepartment of Microbiology and Immunology, Bluemle Life Science Building, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Lingjuan TangDepartment of Microbiology and Immunology, Bluemle Life Science Building, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Paulo J C LinAcuitas Therapeutics, Vancouver, BC V6T 1Z3, Canada.
Ying K TamAcuitas Therapeutics, Vancouver, BC V6T 1Z3, Canada.
Drew WeissmanDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Norbert PardiDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Luis J SigalDepartment of Microbiology and Immunology, Bluemle Life Science Building, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: luis.sigal@jefferson.edu.
Thomas Jefferson University · USUniversity of Pennsylvania · USAcuitas Therapeutics (Canada) · CAUniversity of Minho · PT

Funding

X-Ray Crystallography and Macromolecular CharacterizationP30CA056036 · NCI · THOMAS JEFFERSON UNIVERSITY · PI DANIEL P SILVER · 1995 to 2026
$94.8M
Orthropoxvirus Pathogenesis and VaccinesR01AI065544 · NIAID · THOMAS JEFFERSON UNIVERSITY · PI SIGAL, LUIS J · 2006 to 2016
$5.7M
Lipid nanoparticles as novel adjuvants inducing effective T follicular helper cell and humoral immune responsesR01AI153064 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Michela Locci, Norbert Pardi · 2020 to 2026
$4.2M
Development of Universal Influenza Virus Vaccines Using Nucleoside-Modified Messenger RNAR01AI146101 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI PARDI, NORBERT · 2019 to 2023
$3.1M
Inflammatory monocytes in the draining lymph node of ECTV infected miceR01AI110457 · NIAID · THOMAS JEFFERSON UNIVERSITY · PI SIGAL, LUIS J · 2015 to 2019
$2.3M
Natural Killer Cell Deficiencies in Aging MiceR01AG048602 · NIA · THOMAS JEFFERSON UNIVERSITY · PI SIGAL, LUIS J · 2014 to 2018
$1.8M
Training grant on Vaccines and Immunotherapies for Infectious Diseases and CancerT32AI134646 · NIAID · THOMAS JEFFERSON UNIVERSITY · PI SCHNELL, MATTHIAS JOHANNES, SIGAL, LUIS J · 2018 to 2022
$1.1M
NCI NIH HHS P30 CA056036NIAID NIH HHS R01 AI065544NIAID NIH HHS R01 AI110457NIAID NIH HHS R01 AI146101NIAID NIH HHS R01 AI153064NIAID NIH HHS T32 AI134646NIA NIH HHS R01 AG048602
6 · The paper itself

Abstract

It is well established that memory CD8 T cells protect susceptible strains of mice from mousepox, a lethal viral disease caused by ectromelia virus (ECTV), the murine counterpart to human variola virus. While mRNA vaccines induce protective antibody (Ab) responses, it is unknown whether they also induce protective memory CD8 T cells. We now show that immunization with different doses of unmodified or N(1)-methylpseudouridine-modified mRNA (modified mRNA) in lipid nanoparticles (LNP) encoding the ECTV gene EVM158 induced similarly strong CD8 T cell responses to the epitope TSYKFESV, albeit unmodified mRNA-LNP had adverse effects at the inoculation site. A single immunization with 10 μg modified mRNA-LNP protected most susceptible mice from mousepox, and booster vaccination increased the memory CD8 T cell pool, providing full protection. Moreover, modified mRNA-LNP encoding TSYKFESV appended to green fluorescent protein (GFP) protected against wild-type ECTV infection while lymphocytic choriomeningitis virus glycoprotein (GP) modified mRNA-LNP protected against ECTV expressing GP epitopes. Thus, modified mRNA-LNP can be used to create protective CD8 T cell-based vaccines against viral infections.

Indexed as

AnimalsCD8-Positive T-LymphocytesDrug CompoundingEctromelia, InfectiousEctromelia virusImmunization, SecondaryImmunologic MemoryLiposomesMaleMicemRNA VaccinesNanoparticlesPeptidesPseudouridineViral ProteinsViral Vaccines1-methylpseudouridineLipid NanoparticlesLiposomesmRNA VaccinesPeptidesPseudouridineViral ProteinsViral VaccinesCD8 T cellslipid nanoparticlemodified mRNAmRNA vaccinepoxvirusvirus

Identifiers

PMID33992803
PMCPMC8417516
OpenAlexW3163727330

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.