Evidence map›Paper›PMID 18541651›Full record

ArticleInfection and immunity2008

Constitutive Activation of the PrfA regulon enhances the potency of vaccines based on live-attenuated and killed but metabolically active Listeria monocytogenes strains.

Peter Lauer, Bill Hanson, Edward E Lemmens, Weiqun Liu, William S Luckett, Meredith L Leong, Heather E Allen, Justin Skoble, Keith S Bahjat, Nancy E Freitag and 2 more

Abstract read
In one paragraph

Article in Infection and immunity, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
2.3field-weighted citation impact, top 13% 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

44 citing papers in PubMed, 57 citations in OpenAlex.

  1. Bacteria-Based Nanoprobes for Cancer Therapy.International journal of nanomedicine · 2024
    Review
  2. mBio · 2022
    Article
  3. Review
  4. Review
  5. Article
  6. A Cross-Protective Vaccine Against 4b and 1/2bFrontiers in microbiology · 2020
    Article
  7. Article
  8. A Potent and Effective SuicidalInfection and immunity · 2019
    Article
  9. Article
  10. Innate and Adaptive Immune Responses duringMicrobiology spectrum · 2019
    Article
  11. Article
  12. Vaccines · 2018
    Review
  13. Article
  14. Article
  15. Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  16. Article
  17. Activation of themBio · 2017
    Article
  18. Article
  19. Article
  20. 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

12 authors at 2 institutions in 1 country.

Peter LauerAnza Therapeutics, Inc., Concord, CA 94520, USA. plauer@anzatherapeutics.com
Bill Hanson
Edward E Lemmens
Weiqun Liu
William S Luckett
Meredith L Leong
Heather E Allen
Justin Skoble
Keith S Bahjat
Nancy E Freitag
Dirk G Brockstedt
Thomas W Dubensky
Cerus (United States) · USUniversity of Illinois Chicago · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Recombinant vaccines derived from the facultative intracellular bacterium Listeria monocytogenes are presently undergoing early-stage clinical evaluation in oncology treatment settings. This effort has been stimulated in part due to preclinical results that illustrate potent activation of innate and adaptive immune effectors by L. monocytogenes vaccines, combined with efficacy in rigorous animal models of malignant and infectious disease. Here, we evaluated the immunologic potency of a panel of isogenic vaccine strains that varied only in prfA. PrfA is an intracellularly activated transcription factor that induces expression of virulence genes and encoded heterologous antigens (Ags) in appropriately engineered vaccine strains. Mutant strains with PrfA locked into a constitutively active state are known as PrfA* mutants. We assessed the impacts of three PrfA* mutants, G145S, G155S, and Y63C, on the immunologic potencies of live-attenuated and photochemically inactivated nucleotide excision repair mutant (killed but metabolically active [KBMA]) vaccines. While PrfA* substantially increased Ag expression in strains grown in broth culture, Ag expression levels were equivalent in infected macrophage and dendritic cell lines, conditions that more closely parallel those in the immunized host. However, only the prfA(G155S) allele conferred significantly enhanced vaccine potency to KBMA vaccines. In the KBMA vaccine background, we show that PrfA*(G155S) enhanced functional cellular immunity following an intravenous or intramuscular prime-boost immunization regimen. These results form the basis of a rationale for including the prfA(G155S) allele in future live-attenuated or KBMA L. monocytogenes vaccines advanced to the clinical setting.

Indexed as

Amino Acid SubstitutionAnimalsAntigensAntigens, BacterialBacterial VaccinesFemaleImmunization, SecondaryInjections, IntramuscularInjections, IntravenousLethal Dose 50Listeria monocytogenesListeriosisMiceMice, Inbred BALB CMice, Inbred C57BLMutation, MissenseAntigensAntigens, BacterialBacterial VaccinesPeptide Termination FactorsRecombinant ProteinsVirulence Factors

Identifiers

PMID18541651
PMCPMC2493200
OpenAlexW2121378294

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.