Evidence map›Paper›PMID 40986358›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Preferential apical infection and spread of human metapneumovirus highlights the importance of inhaled delivery of neutralizing monoclonal antibody to treat established infections.

Karthik Tiruthani, Madison P Card, Whitney Wolf, Limei Shen, Alison Schaefer, Marshall Fritz, Kenichi Okuda, Jack R Harkema, Jarrod J Mousa, Raymond J Pickles and 1 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 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

11 authors.

Karthik Tiruthani *Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Madison P Card *University of North Carolina at Chapel Hill Marsico Lung Institute, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.ORCID 0009-0001-5626-5273
Whitney WolfDivision of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Limei ShenDivision of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Alison SchaeferUniversity of North Carolina at Chapel Hill/North Carolina State University Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Marshall FritzDivision of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Kenichi OkudaUniversity of North Carolina at Chapel Hill Marsico Lung Institute, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Jack R HarkemaDepartment of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824.ORCID 0000-0003-4682-0824
Jarrod J MousaDepartment of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL 32306.ORCID 0000-0003-4709-2478
Raymond J PicklesUniversity of North Carolina at Chapel Hill Marsico Lung Institute, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Samuel K LaiDivision of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.ORCID 0000-0003-4721-528X

Funding

Vector CoreP30DK065988 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Scott H Randell · 2004 to 2026
$26.5M
Engineered “muco-trapping” antibodies for inhaled therapy of parainfluenza and human metapneumovirus infectionsR01AI165853 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Samuel Lai, RAYMOND J PICKLES · 2022 to 2026
$3.1M
Mucociliary innate defense mechanism in the human distal airwayR01HL163602 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Kenichi Okuda · 2023 to 2026
$2.4M
SBIR: In vivo validation and IND-enabling development of MM004, a bispecific inhaled immunotherapy for RSV and MPVR44AI157661 · NIAID · MUCOMMUNE, LLC · PI CONE, RICHARD · 2021 to 2024
$2.4M
Aerosol immunotherapy for treatment of human metapneumovirus infectionR43AI149894 · NIAID · MUCOMMUNE, LLC · PI CONE, RICHARD · 2020 to 2020
$262k
HHS | NIH (NIH) R01AI165853HHS | NIH (NIH) R43AI149894HHS | NIH (NIH) R44AI157661NHLBI NIH HHS R01 HL163602NIAID NIH HHS R01 AI165853NIAID NIH HHS R43 AI149894NIAID NIH HHS R44 AI157661NIDDK NIH HHS P30 DK065988UNC | UNC-CH | UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill (UNC Eshelman School of Pharmacy) N/A
6 · The paper itself

Abstract

Human metapneumovirus (hMPV) is a frequent cause of acute respiratory infections in infants, the elderly, and the immunocompromised. No vaccines or treatments are currently available beyond supportive care. Building on our previous work with parainfluenza viruses and respiratory syncytial virus, we investigate the pattern of hMPV infection and spread in polarized and well-differentiated cultures of human airway epithelium (WD-HAE). We found productive infection of WD-HAE requires apical inoculation of hMPV, with infectious spread dependent on progeny viruses shedding into mucus secretions overlaying the apical surface of WD-HAE. A potent neutralizing monoclonal antibodies (mAb) against hMPV fusion protein-mAb364 (also termed MPV364)-prevented initial infection by hMPV and halted spread of established hMPV infection when dosed directly to the apical surface of WD-HAE. Conversely, mAb364 delivered to the basal compartment was unable to curb established infections, even at 100-fold greater concentrations. Intranasal delivery of mAb364 to hamsters with established hMPV infections reduced viral titers by ~four logs within 2 d and alleviated key pathological outcomes of hMPV infection. These results are consistent with hMPV infection and continued spread occurring via the apical surface of the respiratory epithelium, and underscore delivery of neutralizing mAbs to the respiratory tract as an effective intervention against established hMPV infections.

Indexed as

Antibodies, NeutralizingAntibodies, ViralMetapneumovirusParamyxoviridae InfectionsRespiratory Tract InfectionsAdministration, InhalationAnimalsAntibodies, MonoclonalChlorocebus aethiopsDisease Models, AnimalFemaleHumansMaleMesocricetusPrimary Cell CultureRespiratory MucosaAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralViral Fusion Proteinsantibodyantibody deliverymetapneumovirus

Identifiers

PMID40986358
PMCPMC12501197

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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.