Evidence map›Paper›PMID 33895015›Full record

ArticleVaccine2022

Immunisation with the BCG and DTPw vaccines induces different programs of trained immunity in mice.

Natalie E Stevens, Marjolein van Wolfswinkel, Winnie Bao, Feargal J Ryan, Byron Brook, Nelly Amenyogbe, Helen S Marshall, Miriam A Lynn, Tobias R Kollmann, Damon J Tumes and 1 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Vaccine, 2022. 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
0.8field-weighted citation impact, top 30% 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, 11 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

11 authors at 5 institutions in 3 countries.

Natalie E StevensPrecision Medicine Theme, South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA 5000, Australia.
Marjolein van WolfswinkelPrecision Medicine Theme, South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA 5000, Australia; University of Applied Sciences Leiden, Zernikedreef 11, 2333 CK Leiden, the Netherlands.
Winnie BaoDepartment of Peadiatrics, University of British Columbia, 2775 Laurel Street, 10th Floor, Room 10117, Vancouver, BC V5Z 1M9, Canada.
Feargal J RyanPrecision Medicine Theme, South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA 5000, Australia.
Byron BrookDepartment of Experimental Medicine, University of British Columbia, 2775 Laurel Street, 10th Floor, Room 10117, Vancouver, BC V5Z 1M9, Canada.
Nelly AmenyogbeDepartment of Experimental Medicine, University of British Columbia, 2775 Laurel Street, 10th Floor, Room 10117, Vancouver, BC V5Z 1M9, Canada; Telethon Kids Institute, 100 Roberts Road, Subiaco, Western Australia 6008, Australia.
Helen S MarshallVaccinology and Immunology Research Trials Unit, Women's and Children's Hospital, North Adelaide, SA 5006, Australia; Child and Adolescent Health, Robinson Research Institute, The University of Adelaide, North Adelaide, SA 5006, Australia.
Miriam A LynnPrecision Medicine Theme, South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA 5000, Australia.
Tobias R KollmannDepartment of Experimental Medicine, University of British Columbia, 2775 Laurel Street, 10th Floor, Room 10117, Vancouver, BC V5Z 1M9, Canada; Telethon Kids Institute, 100 Roberts Road, Subiaco, Western Australia 6008, Australia.
Damon J TumesPrecision Medicine Theme, South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA 5000, Australia.
David J LynnPrecision Medicine Theme, South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA 5000, Australia; College of Medicine and Public Health, Flinders University, Bedford Park, SA 5042, Australia. Electronic address: david.lynn@sahmri.com.
South Australian Health and Medical Research Institute · AUUniversity of British Columbia · CAFlinders University · AUUniversity of Applied Sciences Leiden · NLWomen's and Children's Hospital · AU

Funding

Transcriptomics to define biomarkers of neonatal vaccine immunogenicityU19AI118608 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI LEVY, OFER · 2017 to 2021
$24.7M
NIAID NIH HHS U19 AI118608
6 · The paper itself

Abstract

In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings. The NSEs associated with BCG have been attributed, in part, to the induction of trained immunity, an epigenetic and metabolic reprograming of innate immune cells, increasing their responsiveness to subsequent microbial encounters. Whether non-live vaccines such as DTPw induce trained immunity is currently poorly understood. Here, we report that immunisation of mice with DTPw induced a unique program of trained immunity in comparison to BCG immunised mice. Altered monocyte and DC cytokine responses were evident in DTPw immunised mice even months after vaccination. Furthermore, splenic cDCs from DTPw immunised mice had altered chromatin accessibility at loci involved in immunity and metabolism, suggesting that these changes were epigenetically mediated. Interestingly, changing the order in which the BCG and DTPw vaccines were co-administered to mice altered subsequent trained immune responses. Given these differences in trained immunity, we also assessed whether administration of these vaccines altered susceptibility to sepsis in two different mouse models. Immunisation with either BCG or a DTPw-containing vaccine prior to the induction of sepsis did not significantly alter survival. Further studies are now needed to more fully investigate the potential consequences of DTPw induced trained immunity in different contexts and to assess whether other non-live vaccines also induce similar changes.

Indexed as

DiphtheriaHaemophilus VaccinesTetanusWhooping CoughAnimalsAntibodies, BacterialBCG VaccineDiphtheria-Tetanus-Pertussis VaccineFemaleImmunizationMiceVaccinationAntibodies, BacterialBCG VaccineDiphtheria-Tetanus-Pertussis VaccineHaemophilus VaccinesDendritic cellsInnate immune memoryTrained immunityVaccinationVaccine nonspecific effects

Identifiers

PMID33895015
PMCPMC12273738
OpenAlexW3157787505

What OpenQuestion holds

Textmetadata
LicenceTDM
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.