Evidence map›Paper›PMID 30911758›Full record

ArticleThe Journal of infectious diseases2019

A Highly Immunogenic, Protective, and Safe Adenovirus-Based Vaccine Expressing Middle East Respiratory Syndrome Coronavirus S1-CD40L Fusion Protein in a Transgenic Human Dipeptidyl Peptidase 4 Mouse Model.

Anwar M Hashem, Abdullah Algaissi, Anurodh Shankar Agrawal, Sawsan S Al-Amri, Rowa Y Alhabbab, Sayed S Sohrab, Abdulrahman S Almasoud, Naif Khalaf Alharbi, Bi-Hung Peng, Marsha Russell and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of infectious diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
8.7field-weighted citation impact, top 1% 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

55 citing papers in PubMed, 76 citations in OpenAlex.

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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 4 institutions in 3 countries.

Anwar M HashemDepartment of Medical Microbiology and Parasitology, Faculty of Medicine.
Abdullah AlgaissiDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston.
Anurodh Shankar AgrawalDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston.
Sawsan S Al-AmriVaccines and Immunotherapy Unit, King Fahd Medical Research Center, Saudi Arabia.
Rowa Y AlhabbabVaccines and Immunotherapy Unit, King Fahd Medical Research Center, Saudi Arabia.
Sayed S SohrabSpecial Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
Abdulrahman S AlmasoudDepartment of Infectious Disease Research, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
Naif Khalaf AlharbiDepartment of Infectious Disease Research, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
Bi-Hung PengDepartment of Neurosciences, Cell Biology, and Anatomy, University of Texas Medical Branch, Galveston.
Marsha RussellCenter for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, Health Canada, Ottawa, Ontario.
Xuguang LiCenter for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, Health Canada, Ottawa, Ontario.
Chien-Te K TsengDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston.
King Abdulaziz University · SAThe University of Texas Medical Branch at Galveston · USHealth Canada · CAKing Abdullah International Medical Research Center · SA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundInfection control measures have played a major role in limiting human/camel-to-human transmission of Middle East respiratory syndrome coronavirus (MERS-CoV); however, development of effective and safe human or camel vaccines is warranted.

methodsWe extended and optimized our previous recombinant adenovirus 5 (rAd5)-based vaccine platform characterized by in vivo amplified and CD40-mediated specific responses to generate MERS-CoV S1 subunit-based vaccine. We generated rAd5 constructs expressing CD40-targeted S1 fusion protein (rAd5-S1/F/CD40L), untargeted S1 (rAd5-S1), and Green Fluorescent Protein (rAd5-GFP), and evaluated their efficacy and safety in human dipeptidyl peptidase 4 transgenic (hDPP4 Tg+) mice.

resultsImmunization of hDPP4 Tg+ mice with a single dose of rAd5-S1/F/CD40L elicited as robust and significant specific immunoglobulin G and neutralizing antibodies as those induced with 2 doses of rAd5-S1. After MERS-CoV challenge, both vaccines conferred complete protection against morbidity and mortality, as evidenced by significantly undetectable/reduced pulmonary viral loads compared to the control group. However, rAd5-S1- but not rAd5-S1/F/CD40L-immunized mice exhibited marked pulmonary perivascular hemorrhage post-MERS-CoV challenge despite the observed protection.

conclusionsIncorporation of CD40L into rAd5-based MERS-CoV S1 vaccine targeting molecule and molecular adjuvants not only enhances immunogenicity and efficacy but also prevents inadvertent pulmonary pathology after viral challenge, thereby offering a promising strategy to enhance safety and potency of vaccines.

Indexed as

Adenoviruses, HumanAdjuvants, ImmunologicAnimalsAntibodies, NeutralizingAntibodies, ViralCD40 LigandCoronavirus InfectionsDipeptidyl Peptidase 4Drug CarriersGenetic VectorsImmunoglobulin GLungMiceMice, TransgenicMiddle East Respiratory Syndrome CoronavirusRecombinant Fusion ProteinsAdjuvants, ImmunologicAntibodies, NeutralizingAntibodies, ViralCD40 LigandDipeptidyl Peptidase 4Drug CarriersImmunoglobulin GRecombinant Fusion ProteinsSpike Glycoprotein, CoronavirusVaccines, SubunitVaccines, SyntheticViral VaccinesadenovirusCD40LimmunopathologyMERS-CoVvaccine

Identifiers

PMID30911758
PMCPMC7107499
OpenAlexW2923337208

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.