Evidence map›Paper›PMID 29398273›Full record

ArticleVaccine2018

The choice of linker for conjugating R848 to inactivated influenza virus determines the stimulatory capacity for innate immune cells.

Marlena M Westcott, Elene A Clemens, Beth C Holbrook, S Bruce King, Martha A Alexander-Miller

Abstract read
In one paragraph

Article in Vaccine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

16 citing papers in PubMed, 15 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

5 authors at 1 institution in 1 country.

Marlena M WestcottDepartment of Microbiology and Immunology, Biotech Place, Wake Forest School of Medicine, 575 N. Patterson Ave., Winston-Salem, NC 27101, USA. Electronic address: mwestcot@wakehealth.edu.
Elene A ClemensDepartment of Microbiology and Immunology, Biotech Place, Wake Forest School of Medicine, 575 N. Patterson Ave., Winston-Salem, NC 27101, USA. Electronic address: eclemens@wakehealth.edu.
Beth C HolbrookDepartment of Microbiology and Immunology, Biotech Place, Wake Forest School of Medicine, 575 N. Patterson Ave., Winston-Salem, NC 27101, USA. Electronic address: bcholbro@wakehealth.edu.
S Bruce KingDepartment of Chemistry, Wake Downtown, Wake Forest University, 455 Vine Street, Winston-Salem, NC 27101, USA. Electronic address: kingsb@wfu.edu.
Martha A Alexander-MillerDepartment of Microbiology and Immunology, Biotech Place, Wake Forest School of Medicine, 575 N. Patterson Ave., Winston-Salem, NC 27101, USA. Electronic address: marthaam@wakehealth.edu.
Wake Forest University · US

Funding

Tumor Tissue CoreP30CA012197 · NCI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Ruben A. Mesa · 1985 to 2026
$55.4M
Vaccination strategies to overcome immune deficiencies in neonatesR01AI098339 · NIAID · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ALEXANDER-MILLER, MARTHA ANN · 2012 to 2015
$2.3M
NCI NIH HHS P30 CA012197NIAID NIH HHS R01 AI098339
6 · The paper itself

Abstract

Inactivated influenza vaccines are not approved for use in infants less than 6 months of age due to poor immunogenicity in that population. While the live attenuated influenza vaccine has the potential to be more immunogenic, it is not an option for infants and other vulnerable populations, including the elderly and immunocompromised individuals due to safety concerns. In an effort to improve the immunogenicity of the inactivated vaccine for use in vulnerable populations, we have used an approach of chemically crosslinking the Toll-like receptor (TLR) 7/8 agonist R848 directly to virus particles. We have reported previously that an R848-conjugated, inactivated vaccine is more effective at inducing adaptive immune responses and protecting against lung pathology in influenza challenged neonatal African green monkeys than is the unmodified counterpart. In the current study, we describe a second generation vaccine that utilizes an amide-sulfhydryl crosslinker with different spacer chemistry and length to couple R848 to virions. The new vaccine has significantly enhanced immunostimulatory activity for murine macrophages and importantly for monocyte derived human dendritic cells. Demonstration of the significant differences in stimulatory activity afforded by modest changes in linker impacts our fundamental view of the design of TLR agonist-antigen vaccines.

Indexed as

Adaptive ImmunityAnimalsDendritic CellsHumansImidazolesInfluenza A virusInfluenza VaccinesMiceRAW 264.7 CellsVaccines, ConjugateVaccines, InactivatedVaccinia virusImidazolesInfluenza VaccinesresiquimodVaccines, ConjugateVaccines, InactivatedAdjuvantDendritic cellInfluenzaR848Toll-like receptorVaccine

Identifiers

PMID29398273
PMCPMC5815857
OpenAlexW2794319127

What OpenQuestion holds

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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.