Evidence map›Paper›PMID 32574095›Full record

ArticleHuman vaccines & immunotherapeutics2020

Small-molecule inhibitors of TBK1 serve as an adjuvant for a plasmid-launched live-attenuated yellow fever vaccine.

Sapna Sharma, Michael A Schmid, Lorena Sanchez Felipe, Jana Grenelle, Suzanne J F Kaptein, Lotte Coelmont, Johan Neyts, Kai Dallmeier

Open access · bronzeAbstract read
In one paragraph

Article in Human vaccines & immunotherapeutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

6 citing papers in PubMed, 14 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

8 authors at 1 institution in 2 countries.

Sapna SharmaKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery Group , Leuven, Belgium.ORCID 0000-0003-3493-252X
Michael A SchmidKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery Group , Leuven, Belgium.ORCID 0000-0002-1137-9322
Lorena Sanchez FelipeKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery Group , Leuven, Belgium.ORCID 0000-0002-6928-0931
Jana GrenelleKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery Group , Leuven, Belgium.
Suzanne J F KapteinKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery Group , Leuven, Belgium.ORCID 0000-0002-7935-0219
Lotte CoelmontKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery Group , Leuven, Belgium.ORCID 0000-0002-7888-4534
Johan NeytsKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery Group , Leuven, Belgium.ORCID 0000-0002-0033-7514
Kai DallmeierKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Molecular Vaccinology and Vaccine Discovery Group , Leuven, Belgium.ORCID 0000-0002-8117-9166
Rega Institute for Medical Research · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Plasmid-launched live-attenuated vaccines (PLLAV), also called infectious DNA (iDNA) vaccines, combine the assets of genetic immunization with the potency of replication-competent live viral vaccines. However, due to their origin as bacterial plasmid DNA, efficient delivery of PLLAV may be hampered by innate signaling pathways such as the cGAS-STING-mediated sensing of cytosolic DNA, resulting in an unfavorable proinflammatory and antiviral response locally at the site of immunization. Employing several complementary cell-based systems and using the yellow fever vaccine (YF17D) and the respective PLLAV-YF17D, we screened a panel of small molecules known to interfere with antiviral signaling for their proviral activity and identified two potent inhibitors of the TANK-binding kinase 1 (TBK1), BX795 and CYT387, to enhance YF17D replication and hence efficacy of PLLAV-YF17D transfection. In tissue culture, BX795 could fully revert the block that plasmid transfection poses on YF17D infection in a type I interferon dependent manner, as confirmed by (i) a marked change in gene expression signatures, (ii) a rescue of full YF17D replication, and (iii) a massively increased virus yield. Inhibitors of TBK1 may hence be considered an adjuvant to potentiate novel PLLAV vaccines, which might boost PLLAV delivery toward their use

Indexed as

Vaccines, DNAViral VaccinesYellow Fever VaccinePlasmidsVaccines, AttenuatedVaccines, AttenuatedVaccines, DNAViral VaccinesYellow Fever VaccineBX795innate antiviral immunityinterferon signalingPlasmid-launched live-attenuated vaccineproviralself-amplifying RNA vaccineTBK1

Identifiers

PMID32574095
PMCPMC7553677
OpenAlexW3036939412

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.