Evidence map›Paper›PMID 18958172›Full record

ArticlePloS one2008

Nasal delivery of an adenovirus-based vaccine bypasses pre-existing immunity to the vaccine carrier and improves the immune response in mice.

Maria A Croyle, Ami Patel, Kaylie N Tran, Michael Gray, Yi Zhang, James E Strong, Heinz Feldmann, Gary P Kobinger

Open access · goldAbstract readEvaluation Study
In one paragraph

Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.

0numbers the graph read from it
0cells of the map it votes in
114citing papers in PubMed
5.9field-weighted citation impact, top 4% 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

114 citing papers in PubMed, 171 citations in OpenAlex.

  1. Trial
  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. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Developing the next-generation of adenoviral vector vaccines.Human vaccines & immunotherapeutics · 2025
    Review
  10. Article
  11. Effect of heterologous intranasal iNCOVACCCommunications medicine · 2025
    Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Construction and application of adenoviral vectors.Molecular therapy. Nucleic acids · 2023
    Review
  19. Article
  20. Review

54 more citing papers are in PubMed but not listed here.

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

8 authors at 4 institutions in 2 countries.

Maria A CroyleDivision of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, Texas, USA.
Ami Patel
Kaylie N Tran
Michael Gray
Yi Zhang
James E Strong
Heinz Feldmann
Gary P Kobinger
University of Manitoba · CAPublic Health Agency of Canada · CAMichigan United · USThe University of Texas at Austin · US

Funding

Viral Hemorrhagic Fevers: Disease Modeling and TransmissionZIAAI001089 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI FELDMANN, HEINRICH · 2009 to 2025
$50.7M
6 · The paper itself

Abstract

Pre-existing immunity to human adenovirus serotype 5 (Ad5) is common in the general population. Bypassing pre-existing immunity could maximize Ad5 vaccine efficacy. Vaccination by the intramuscular (I.M.), nasal (I.N.) or oral (P.O.) route with Ad5 expressing Ebola Zaire glycoprotein (Ad5-ZGP) fully protected naïve mice against lethal challenge with Ebola. In the presence of pre-existing immunity, only mice vaccinated I.N. survived. The frequency of IFN-gamma+ CD8+ T cells was reduced by 80% and by 15% in animals vaccinated by the I.M. and P.O. routes respectively. Neutralizing antibodies could not be detected in serum from either treatment group. Pre-existing immunity did not compromise the frequency of IFN-gamma+ CD8+ T cells (3.9+/-1% naïve vs. 3.6+/-1% pre-existing immunity, PEI) nor anti-Ebola neutralizing antibody (NAB, 40+/-10 reciprocal dilution, both groups). The number of INF-gamma+ CD8+ cells detected in bronchioalveolar lavage fluid (BAL) after I.N. immunization was not compromised by pre-existing immunity to Ad5 (146+/-14, naïve vs. 120+/-16 SFC/million MNCs, PEI). However, pre-existing immunity reduced NAB levels in BAL by approximately 25% in this group. To improve the immune response after oral vaccination, the Ad5-based vaccine was PEGylated. Mice given the modified vaccine did not survive challenge and had reduced levels of IFN-gamma+ CD8+ T cells 10 days after administration (0.3+/-0.3% PEG vs. 1.7+/-0.5% unmodified). PEGylation did increase NAB levels 2-fold. These results provide some insight about the degree of T and B cell mediated immunity necessary for protection against Ebola virus and suggest that modification of the virus capsid can influence the type of immune response elicited by an Ad5-based vaccine.

Indexed as

AdenoviridaeAdministration, IntranasalAnimalsAntibody FormationBronchoalveolar Lavage FluidDrug Delivery SystemsEbola VaccinesEbolavirusHemorrhagic Fever, EbolaImmunity, MucosalImmunotherapy, ActiveMiceMice, Inbred C57BLPolyethylene GlycolsSurvival AnalysisVirosomesEbola VaccinesPolyethylene GlycolsVirosomes

Identifiers

PMID18958172
PMCPMC2569416
OpenAlexW2054258731

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.