Evidence map›Paper›PMID 34485597›Full record

ArticleMolecular therapy. Methods & clinical development2021

Antigen modifications improve nucleoside-modified mRNA-based influenza virus vaccines in mice.

Alec W Freyn, Matthew Pine, Victoria C Rosado, Marcel Benz, Hiromi Muramatsu, Mitchell Beattie, Ying K Tam, Florian Krammer, Peter Palese, Raffael Nachbagauer and 2 more

Open access · goldAbstract read
In one paragraph

Article in Molecular therapy. Methods & clinical development, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

33 citing papers in PubMed, 38 citations in OpenAlex.

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  20. Advanced delivery systems for peptide antibiotics.Advanced drug delivery reviews · 2023
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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

12 authors at 3 institutions in 2 countries.

Alec W FreynDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Matthew PineDepartment of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Victoria C RosadoDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Marcel BenzDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Hiromi MuramatsuDepartment of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Mitchell BeattieAcuitas Therapeutics, Vancouver, BC V6T 1Z3, Canada.
Ying K TamAcuitas Therapeutics, Vancouver, BC V6T 1Z3, Canada.
Florian KrammerDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Peter PaleseDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Raffael NachbagauerDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Meagan McMahonDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Norbert PardiDepartment of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Icahn School of Medicine at Mount Sinai · USUniversity of Pennsylvania · USAcuitas Therapeutics (Canada) · CA

Funding

COLLABORATIVE INFLUENZA VACCINE INNOVATION CENTER: UNIVERSAL INFLUENZA VACCINE RESEARCH75N93019C00051 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KRAMMER, FLORIAN · 2019 to 2025
$105.4M
Toward a Universal Influenza Virus VaccineP01AI097092 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI PALESE, PETER · 2012 to 2022
$17.6M
TRAINING PROGRAM: MECHANISMS OF VIRUS-HOST INTERACTIONST32AI007647 · NIAID · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI Domenico Tortorella · 2000 to 2026
$11.5M
Evaluation of the FcgR mechanisms in the antibody-dependent enhancement of SARS-CoV-2 infectionR01AI145870 · NIAID · ROCKEFELLER UNIVERSITY · PI Peter Palese, JEFFREY Victor RAVETCH · 2019 to 2026
$8.4M
Development of Universal Influenza Virus Vaccines Using Nucleoside-Modified Messenger RNAR01AI146101 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI PARDI, NORBERT · 2019 to 2023
$3.1M
NIAID NIH HHS 75N93019C00051NIAID NIH HHS HHSN272201400008CNIAID NIH HHS P01 AI097092NIAID NIH HHS R01 AI145870NIAID NIH HHS R01 AI146101NIAID NIH HHS T32 AI007647
6 · The paper itself

Abstract

Nucleoside-modified, lipid nanoparticle-encapsulated mRNAs have recently emerged as suitable vaccines for influenza viruses and other pathogens in part because the platform allows delivery of multiple antigens in a single immunization. mRNA vaccines allow for easy antigen modification, enabling rapid iterative design. We studied protein modifications such as mutating functional sites, changing secretion potential, and altering protein conformation, which could improve the safety and/or potency of mRNA-based influenza virus vaccines. Mice were vaccinated intradermally with wild-type or mutant constructs of influenza virus hemagglutinin (HA), neuraminidase (NA), matrix protein 2 (M2), nucleoprotein (NP), or matrix protein 1 (M1). Membrane-bound HA constructs elicited more potent and protective antibody responses than secreted forms. Altering the catalytic site of NA to reduce enzymatic activity decreased reactogenicity while protective immunity was maintained. Disruption of M2 ion channel activity improved immunogenicity and protective efficacy. A comparison of internal proteins NP and M1 revealed the superiority of NP in conferring protection from influenza virus challenge. These findings support the use of the nucleoside-modified mRNA platform for guided antigen design for influenza virus with extension to other pathogens.

Indexed as

antibodyantigenengineeringinfluenzamRNAnucleoside-modifiedoptimizationuniversalvaccine

Identifiers

PMID34485597
PMCPMC8390451
OpenAlexW3168161702

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.