Evidence map›Paper›PMID 39489918›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024

Enhanced mucosal SARS-CoV-2 immunity after heterologous intramuscular mRNA prime/intranasal protein boost vaccination with a combination adjuvant.

Gabriel Laghlali, Matthew J Wiest, Dilara Karadag, Prajakta Warang, Jessica J O'Konek, Lauren A Chang, Seok-Chan Park, Vivian Yan, Mohammad Farazuddin, Katarzyna W Janczak and 4 more

Abstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing 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

22 citing papers in PubMed.

  1. How vaccine research took me on an international journey.Human vaccines & immunotherapeutics · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Gabriel LaghlaliDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pharmaceutics, Ghent University, Ghent, Belgium.
Matthew J WiestDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI, USA.
Dilara KaradagDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI, USA.
Prajakta WarangDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Jessica J O'KonekDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI, USA; Mary H. Weiser Food Allergy Center, University of Michigan Medical School, Ann Arbor, MI, USA.
Lauren A ChangDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Seok-Chan ParkDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Vivian YanDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Mohammad FarazuddinDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI, USA; Mary H. Weiser Food Allergy Center, University of Michigan Medical School, Ann Arbor, MI, USA.
Katarzyna W JanczakDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI, USA; Mary H. Weiser Food Allergy Center, University of Michigan Medical School, Ann Arbor, MI, USA.
Adolfo García-SastreDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
James R BakerDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI, USA; Mary H. Weiser Food Allergy Center, University of Michigan Medical School, Ann Arbor, MI, USA.
Pamela T WongDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI, USA; Mary H. Weiser Food Allergy Center, University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address: ptw@umich.edu.
Michael SchotsaertDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: michael.schotsaert@mssm.edu.

Funding

SARS-CoV adaptations through a Systems Biology Lens (SYBIL)U19AI135972 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Adolfo Garcia-Sastre · 2018 to 2026
$27.2M
Combined adjuvant approaches for enhancement of SARS-CoV-2 vaccine efficacyR01AI160706 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SCHOTSAERT, MICHAEL, WONG, PAMELA TINMOI · 2022 to 2025
$2.9M
Strengthening the ISMMS research and response capabilities for pathogens of pandemic potentialG20AI174733 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ALBRECHT, RANDY A. · 2022 to 2022
$2.3M
Experimental and natural SARS-CoV-2 infection of the human pancreasR01DK130425 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HOMANN, DIRK, SCHOTSAERT, MICHAEL · 2021 to 2023
$1.3M
Adjuvant strategies for universal and multiseasonal influenza vaccine candidates in the context of pre-existing immunityR21AI176069 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI SCHOTSAERT, MICHAEL, WONG, PAMELA TINMOI · 2023 to 2024
$466k
NIAID NIH HHS G20 AI174733NIAID NIH HHS R01 AI160706NIAID NIH HHS R21 AI176069NIAID NIH HHS U19 AI135972NIDDK NIH HHS R01 DK130425
6 · The paper itself

Abstract

Current COVID-19 mRNA vaccines delivered intramuscularly (IM) induce effective systemic immunity, but with suboptimal immunity at mucosal sites, limiting their ability to impart sterilizing immunity. There is strong interest in rerouting immune responses induced in the periphery by parenteral vaccination to the portal entry site of respiratory viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), by mucosal vaccination. We previously demonstrated the combination adjuvant, NE/IVT, consisting of a nanoemulsion (NE) and an RNA-based RIG-I agonist (IVT) induces potent systemic and mucosal immune responses in protein-based SARS-CoV-2 vaccines administered intranasally (IN). Herein, we demonstrate priming IM with mRNA followed by heterologous IN boosting with NE/IVT adjuvanted recombinant antigen induces strong mucosal and systemic antibody responses and enhances antigen-specific T cell responses in mucosa-draining lymph nodes compared to IM/IM and IN/IN prime/boost regimens. While all regimens induced cross-neutralizing antibodies against divergent variants and sterilizing immunity in the lungs of challenged mice, mucosal vaccination, either as homologous prime/boost or heterologous IN boost after IM mRNA prime, was required to impart sterilizing immunity in the upper respiratory tract. Our data demonstrate the benefit of hybrid regimens whereby strong immune responses primed via IM vaccination are rerouted by IN vaccination to mucosal sites to provide optimal protection against SARS-CoV-2.

Indexed as

Administration, IntranasalAntibodies, ViralCOVID-19COVID-19 VaccinesImmunity, MucosalSARS-CoV-2Adjuvants, ImmunologicAdjuvants, VaccineAnimalsAntibodies, NeutralizingFemaleHumansImmunization, SecondaryInjections, IntramuscularMicemRNA VaccinesAdjuvants, ImmunologicAdjuvants, VaccineAntibodies, NeutralizingAntibodies, ViralCOVID-19 VaccinesmRNA VaccinesSpike Glycoprotein, Coronavirusintranasal vaccinationmRNA vaccinesmucosal adjuvantsmucosal immunizationprime/pullSARS-Cov-2tissue-resident memory T cells

Identifiers

PMID39489918
PMCPMC11638833

What OpenQuestion holds

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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.