Evidence map›Paper›PMID 39589869›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2024

Staggered immunization with mRNA vaccines encoding SARS-CoV-2 polymerase or spike antigens broadens the T cell epitope repertoire.

Evan R Abt, Alex K Lam, Miyako Noguchi, Khalid Rashid, Jami McLaughlin, Pu-Lin Teng, Wendy Tran, Donghui Cheng, Pavlo A Nesterenko, Zhiyuan Mao and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Designing 5' UTR sequences improves the capacity of mRNA therapeutics in preclinical models of aging and obesity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  2. Article
  3. 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

21 authors.

Evan R Abt *Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA 90095.ORCID 0000-0002-3160-7134
Alex K Lam *Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA 90095.ORCID 0000-0003-2879-719X
Miyako NoguchiDepartment of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095.
Khalid RashidDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA 90095.
Jami McLaughlinDepartment of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095.
Pu-Lin TengDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA 90095.
Wendy TranDepartment of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095.
Donghui ChengDepartment of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095.
Pavlo A NesterenkoDepartment of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095.
Zhiyuan MaoDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA 90095.
Amanda L CreechDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA 90095.
Giselle Burton SojoDepartment of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095.
Arjit Vijey JeyachandranDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA 90095.
Ying K TamAcuitas Therapeutics, Vancouver, BC V6T 1Z3, Canada.ORCID 0000-0002-4083-5251
Jill E HenleyDepartment of Molecular Microbiology and Immunology, The Hastings and Wright Laboratories, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089.
Lucio ComaiDepartment of Molecular Microbiology and Immunology, The Hastings and Wright Laboratories, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089.
Norbert PardiDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.ORCID 0000-0003-1008-6242
Vaithilingaraja ArumugaswamiDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA 90095.ORCID 0000-0002-6872-5118
Owen N WitteDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA 90095.ORCID 0000-0003-4461-4533
Caius G RaduDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA 90095.ORCID 0000-0002-9338-5397
Ting-Ting WuDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA 90095.

Funding

UCLA-Caltech Medical Scientist Training ProgramT32GM008042 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AJIJOLA, OLUJIMI A, DAWSON, DAVID WAYNE · 1985 to 2023
$29.9M
UCLA Tumor Immunology Training ProgramT32CA009120 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Steven M. Dubinett, MICHAEL A TEITELL · 1985 to 2026
$10.3M
Leveraging Vulnerabilities Induced by STING Activation in Pancreatic CancerR01CA250529 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DONAHUE, TIMOTHY R, RADU, CAIUS GABRIEL · 2021 to 2025
$3.1M
California HIV/AIDS Research Program (CHRP) H22BD4466HHS | NIH | National Cancer Institute (NCI) 1R01CA250529-01A1NCI NIH HHS R01 CA250529NCI NIH HHS T32 CA009120NIGMS NIH HHS T32 GM008042
6 · The paper itself

Abstract

Combining a T cell-targeting mRNA vaccine encoding the conserved SARS-CoV-2 RNA-dependent RNA polymerase, RdRp, with a Spike-encoding mRNA vaccine may offer an additional pathway toward COVID-19 protection. Here, we show that a nucleoside-modified RdRp mRNA vaccine raises robust and durable CD8+ T cell responses in mice. Immunization drives a CD8+ T cell response enriched toward a specific RdRp epitope. Unexpectedly, coadministration of mRNA vaccines encoding RdRp or the Spike Receptor Binding Domain (RBD) dampens RBD-specific immune responses. Contralateral administration reduces the suppression of RBD-specific T cell responses while type I interferon signaling blockade restores RBD-specific antibodies. A staggered immunization strategy maintains both RBD vaccine-mediated antibody and T cell responses as well as protection against lethal SARS-CoV-2 challenge in human ACE2 transgenic mice. In HLA-A2.1 transgenic mice, the RdRp vaccine elicits CD8+ T cell responses against HLA-A*02:01-restricted epitopes recognized by human donor T cells. These results highlight RdRp as a candidate antigen for COVID-19 vaccines. The findings also offer insights into crafting effective multivalent mRNA vaccines to broaden CD8+ T cell responses against SARS-CoV-2 and potentially other viruses with pandemic potential.

Indexed as

CD8-Positive T-LymphocytesCOVID-19COVID-19 VaccinesEpitopes, T-LymphocyteMice, TransgenicmRNA VaccinesSARS-CoV-2Spike Glycoprotein, CoronavirusAngiotensin-Converting Enzyme 2AnimalsAntibodies, ViralFemaleHLA-A2 AntigenHumansImmunizationMiceAngiotensin-Converting Enzyme 2Antibodies, ViralCOVID-19 VaccinesEpitopes, T-LymphocyteHLA-A2 AntigenmRNA VaccinesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2Vaccines, Syntheticanti-pathogen T cell responseinterferon signalingmRNA vaccinesSARS-CoV-2T cell receptor specificity

Identifiers

PMID39589869
PMCPMC11626164

What OpenQuestion holds

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LicenceCC BY
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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.