Evidence map›Paper›PMID 26245825›Full record

ArticleJournal of biomedical science2015

Recombinant lipoprotein-based vaccine candidates against C. difficile infections.

Jui-Hsin Huang, Chia-Wei Wu, Shu-Pei Lien, Chih-Hsiang Leng, Kuang-Nan Hsiao, Shih-Jen Liu, Hsin-Wei Chen, Leung-Kei Siu, Pele Chong

Open access · diamondAbstract read
In one paragraph

Article in Journal of biomedical science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

8 citing papers in PubMed, 18 citations in OpenAlex.

  1. Review
  2. Article
  3. Vaccination therapy for inflammatory bowel disease.Human vaccines & immunotherapeutics · 2023
    Review
  4. Article
  5. Review
  6. Lipoprotein-based drug delivery.Advanced drug delivery reviews · 2020
    Review
  7. Article
  8. Article
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 at 2 institutions in 1 country.

Jui-Hsin HuangVaccine R&D Center, National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan. 981046@nhri.org.tw.
Chia-Wei WuVaccine R&D Center, National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan. startup@nhri.org.tw.
Shu-Pei LienVaccine R&D Center, National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan. lenharry@nhri.org.tw.
Chih-Hsiang LengVaccine R&D Center, National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan. leoleng@nhri.org.tw.
Kuang-Nan HsiaoVaccine R&D Center, National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan. sunnyboy@nhri.org.tw.
Shih-Jen LiuVaccine R&D Center, National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan. levent@nhri.org.tw.
Hsin-Wei ChenVaccine R&D Center, National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan. chenhw@nhri.org.tw.
Leung-Kei SiuVaccine R&D Center, National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan. lksiu@nhri.org.tw.
Pele ChongVaccine R&D Center, National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan. pelechong@nhri.org.tw.
National Health Research Institutes · TWNational Defense Medical Center · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOpportunistically nosocomial infections in hospitalized patients are often related to Clostridium difficile infections (CDI) due to disruption of the intestinal micro-flora by antibiotic therapies during hospitalization. Clostridial exotoxins A and B (TcdA and TcdB) specifically bind to unknown glycoprotein(s) in the host intestine, disrupt the intestinal barrier leading to acute inflammation and diarrhea. The C-terminal receptor binding domain of TcdA (A-rRBD) has been shown to elicit antibody responses that neutralize TcdA toxicity in Vero cell cytotoxicity assays, but not effectively protect hamsters against a lethal dose challenge of C. difficile spores. To develop an effective recombinant subunit vaccine against CDI, A-rRBD was lipidated (rlipoA-RBD) as a rational design to contain an intrinsic adjuvant, a toll-like receptor 2 agonist and expressed in Escherichia coli.

resultsThe purified rlipoA-RBD was characterized immunologically and found to have the following properties: (a) mice, hamsters and rabbits vaccinated with 3 μg of rlipoA-RBD produced strong antibody responses that neutralized TcdA toxicity in Vero cell cytotoxicity assays; furthermore, the neutralization titer was comparable to those obtained from antisera immunized either with 10 μg of TcdA toxoid or 30 μg of A-rRBD; (b) rlipoA-RBD elicited immune responses and protected mice from TcdA challenge, but offered insignificant protection (10 to 20 %) against C. difficile spores challenge in hamster models; (c) only rlipoA-RBD formulated with B-rRBD consistently confers protection (90 to 100 %) in the hamster challenge model; and (d) rlipoA-RBD was found to be 10-fold more potent than A-rRBD as an adjuvant to enhancing immune responses against a poor antigen such as ovalbumin.

conclusionThese results indicate that rlipoA-RBD formulated with B-rRBD could be an excellent vaccine candidate for preclinical studies and future clinical trials.

Indexed as

AnimalsBacterial ToxinsBacterial VaccinesChlorocebus aethiopsClostridioides difficileCricetinaeEnterocolitis, PseudomembranousEnterotoxinsLipoproteinsMiceMice, Inbred BALB CRabbitsRecombinant Fusion ProteinsVero CellsBacterial ToxinsBacterial VaccinesClostridium difficile lethal toxin BEnterotoxinsLipoproteinsRecombinant Fusion ProteinstcdA protein, Clostridium difficile

Identifiers

PMID26245825
PMCPMC4527207
OpenAlexW1927212604

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.