Evidence map›Paper›PMID 25517089›Full record

ArticleHuman vaccines & immunotherapeutics2014

Partial pathogen protection by tick-bite sensitization and epitope recognition in peptide-immunized HLA DR3 transgenic mice.

Wendy M C Shattuck, Megan C Dyer, Joe Desrosiers, Loren D Fast, Frances E Terry, William D Martin, Leonard Moise, Anne S De Groot, Thomas N Mather

Abstract read
In one paragraph

Article in Human vaccines & immunotherapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
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

9 authors.

Wendy M C Shattucka Center for Vector-Borne Disease ; University of Rhode Island ; Kingston , RI USA.
Megan C Dyer
Joe Desrosiers
Loren D Fast
Frances E Terry
William D Martin
Leonard Moise
Anne S De Groot
Thomas N Mather

Funding

TRIAD Scientific Core: TRIAD ToolkitU19AI082642 · NIAID · UNIVERSITY OF RHODE ISLAND · PI MOISE, LEONARD · 2009 to 2013
$13.0M
NIAID NIH HHS AI082642
6 · The paper itself

Abstract

Ticks are notorious vectors of disease for humans, and many species of ticks transmit multiple pathogens, sometimes in the same tick bite. Accordingly, a broad-spectrum vaccine that targets vector ticks and pathogen transmission at the tick/host interface, rather than multiple vaccines against every possible tickborne pathogen, could become an important tool for resolving an emerging public health crisis. The concept for such a tick protective vaccine comes from observations of an acquired tick resistance (ATR) that can develop in non-natural hosts of ticks following sensitization to tick salivary components. Mice are commonly used as models to study immune responses to human pathogens but normal mice are natural hosts for many species of ticks and fail to develop ATR. We evaluated HLA DR3 transgenic (tg) "humanized" mice as a potential model of ATR and assessed the possibility of using this animal model for tick protective vaccine discovery studies. Serial tick infestations with pathogen-free Ixodes scapularis ticks were used to tick-bite sensitize HLA DR3 tg mice. Sensitization resulted in a cytokine skew favoring a Th2 bias as well as partial (57%) protection to infection with Lyme disease spirochetes (Borrelia burgdorferi) following infected tick challenge when compared to tick naïve counterparts. I. scapularis salivary gland homogenate (SGH) and a group of immunoinformatic-predicted T cell epitopes identified from the I. scapularis salivary transcriptome were used separately to vaccinate HLA DR3 tg mice, and these mice also were assessed for both pathogen protection and epitope recognition. Reduced pathogen transmission along with a Th2 skew resulted from SGH vaccination, while no significant protection and a possible T regulatory bias was seen in epitope-vaccinated mice. This study provides the first proof-of-concept for using HLA DR tg "humanized" mice for studying the potential tick protective effects of immunoinformatic- or otherwise-derived tick salivary components as tickborne disease vaccines.

Indexed as

AnimalsBorrelia burgdorferiDisease VectorsEpitopes, T-LymphocyteFemaleHLA-DR3 AntigenIxodesLyme DiseaseMiceMice, Inbred C57BLMice, TransgenicSalivary GlandsTh2 CellsVaccinationVaccines, SubunitEpitopes, T-LymphocyteHLA-DR3 AntigenVaccines, SubunitATR, Acquired tick resistanceB6, C57BL/6Bb, Borrelia burgdorferi; Mn, Mus musculusConA, Concanavalin AEpiMatrixepitope-based vaccineepitope discoveryHLA DR3, Human leukocyte antigen, D related 3IFN-γ, Interferon gammaIL-4, Interleukin-4immunizationimmunoinformaticIxodes scapularisLPP, Liposomal peptide poolLyme diseaseNPP, Naked peptide poolNR, No responsesalivary glandSFC, Spot forming cellsSGH, Salivary gland homogenateTBD, Tickborne diseasetg, Transgenictick protective vaccinetransgenic mouse model

Identifiers

PMID25517089
PMCPMC5443055

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Registered trials

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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.