Evidence map›Paper›PMID 37085458›Full record

ArticleVaccine2023

Intranasal administration of adenoviral vaccines expressing SARS-CoV-2 spike protein improves vaccine immunity in mouse models.

Tobias L Freitag, Riku Fagerlund, Nihay Laham Karam, Veli-Matti Leppänen, Hasan Ugurlu, Ravi Kant, Petri Mäkinen, Ahmed Tawfek, Sawan Kumar Jha, Tomas Strandin and 17 more

Open access · hybridAbstract read
In one paragraph

Article in Vaccine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

8 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. An adenoviral-vectored vaccine protects mice against aerosol challenge with Yersinia pestis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  3. Review
  4. Article
  5. Review
  6. Article
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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

27 authors at 5 institutions in 2 countries.

Tobias L FreitagTranslational Immunology Research Program, Faculty of Medicine, University of Helsinki, Finland; Department of Bacteriology and Immunology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Riku FagerlundDepartment of Virology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Nihay Laham KaramA.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
Veli-Matti LeppänenWihuri Research Institute, Biomedicum Helsinki, Helsinki, Finland; Translational Cancer Medicine Program, University of Helsinki, Helsinki, Finland.
Hasan UgurluDepartment of Virology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Ravi KantDepartment of Virology, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
Petri MäkinenA.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
Ahmed TawfekA.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
Sawan Kumar JhaWihuri Research Institute, Biomedicum Helsinki, Helsinki, Finland; Translational Cancer Medicine Program, University of Helsinki, Helsinki, Finland.
Tomas StrandinDepartment of Virology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Katarzyna LeskinenTranslational Immunology Research Program, Faculty of Medicine, University of Helsinki, Finland; Folkhälsan Research Center, Helsinki, Finland.
Jussi HepojokiDepartment of Virology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Tapio KestiDepartment of Virology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Lauri KareinenDepartment of Virology, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
Suvi KuivanenDepartment of Virology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Emma KoivulehtoA.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
Aino SormunenA.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
Svetlana LaidinenA.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
Ayman KhattabTranslational Immunology Research Program, Faculty of Medicine, University of Helsinki, Finland; Department of Bacteriology and Immunology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Päivi SaavalainenTranslational Immunology Research Program, Faculty of Medicine, University of Helsinki, Finland; Folkhälsan Research Center, Helsinki, Finland.
Seppo MeriTranslational Immunology Research Program, Faculty of Medicine, University of Helsinki, Finland; Department of Bacteriology and Immunology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Anja KiparDepartment of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland; Laboratory for Animal Model Pathology, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland.
Tarja SironenDepartment of Virology, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
Olli VapalahtiDepartment of Virology, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland; Diagnostic Center, Helsinki University Hospital, Helsinki, Finland.
Kari AlitaloWihuri Research Institute, Biomedicum Helsinki, Helsinki, Finland; Translational Cancer Medicine Program, University of Helsinki, Helsinki, Finland.
Seppo Ylä-HerttualaA.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
Kalle SakselaDepartment of Virology, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Diagnostic Center, Helsinki University Hospital, Helsinki, Finland. Electronic address: kalle.saksela@helsinki.fi.
University of Helsinki · FIUniversity of Eastern Finland · FIUniversity of Zurich · CHFolkhälsans Forskningscentrum · FIWihuri Research Institute · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The ongoing SARS-CoV-2 pandemic is controlled but not halted by public health measures and mass vaccination strategies which have exclusively relied on intramuscular vaccines. Intranasal vaccines can prime or recruit to the respiratory epithelium mucosal immune cells capable of preventing infection. Here we report a comprehensive series of studies on this concept using various mouse models, including HLA class II-humanized transgenic strains. We found that a single intranasal (i.n.) dose of serotype-5 adenoviral vectors expressing either the receptor binding domain (Ad5-RBD) or the complete ectodomain (Ad5-S) of the SARS-CoV-2 spike protein was effective in inducing i) serum and bronchoalveolar lavage (BAL) anti-spike IgA and IgG, ii) robust SARS-CoV-2-neutralizing activity in the serum and BAL, iii) rigorous spike-directed T helper 1 cell/cytotoxic T cell immunity, and iv) protection of mice from a challenge with the SARS-CoV-2 beta variant. Intramuscular (i.m.) Ad5-RBD or Ad5-S administration did not induce serum or BAL IgA, and resulted in lower neutralizing titers in the serum. Moreover, prior immunity induced by an intramuscular mRNA vaccine could be potently enhanced and modulated towards a mucosal IgA response by an i.n. Ad5-S booster. Notably, Ad5 DNA was found in the liver or spleen after i.m. but not i.n. administration, indicating a lack of systemic spread of the vaccine vector, which has been associated with a risk of thrombotic thrombocytopenia. Unlike in otherwise genetically identical HLA-DQ6 mice, in HLA-DQ8 mice Ad5-RBD vaccine was inferior to Ad5-S, suggesting that the RBD fragment does not contain a sufficient collection of helper-T cell epitopes to constitute an optimal vaccine antigen. Our data add to previous promising preclinical results on intranasal SARS-CoV-2 vaccination and support the potential of this approach to elicit mucosal immunity for preventing transmission of SARS-CoV-2.

Indexed as

COVID-19Viral VaccinesAdministration, IntranasalAnimalsAntibodies, NeutralizingAntibodies, ViralCOVID-19 VaccinesDisease Models, AnimalHumansImmunoglobulin AMiceSARS-CoV-2Spike Glycoprotein, CoronavirusAntibodies, NeutralizingAntibodies, ViralCOVID-19 VaccinesImmunoglobulin ASpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2Viral VaccinesAdenoviral vectorCOVID-19Intranasal vaccinationMucosal immunitySARS-CoV-2

Identifiers

PMID37085458
PMCPMC10114927
OpenAlexW4366742220

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.