Evidence map›Paper›PMID 35533496›Full record

Trial reportEBioMedicine2022

A CD4+ TNF+ monofunctional memory T-cell response to BCG vaccination is associated with Mycobacterium tuberculosis infection in infants exposed to HIV.

Alex J Warr, Christine Anterasian, Javeed A Shah, Stephen C De Rosa, Felicia K Nguyen, Elizabeth Maleche-Obimbo, Lisa M Cranmer, Daniel Matemo, Jerphason Mecha, John Kinuthia and 3 more

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in EBioMedicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
0.7field-weighted citation impact, top 31% 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

4 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. 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

13 authors at 4 institutions in 2 countries.

Alex J WarrDepartment of Medicine, University of Washington, 750 Republican St, Seattle, WA 98109, USA. Electronic address: alex.warr@bcm.edu.
Christine AnterasianDepartment of Pediatrics, University of Washington, 4800 Sand Point Way NE, Seattle, WA 98105, USA.
Javeed A ShahDepartment of Medicine, University of Washington, 750 Republican St, Seattle, WA 98109, USA; Veteran Affairs Puget Sound Healthcare System, 1660 South Columbian Way, Seattle, WA 98108, USA.
Stephen C De RosaVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave North, E4-200, Seattle, WA 98109, USA; Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific St, Seattle, WA 98195, USA.
Felicia K NguyenDepartment of Medicine, University of Washington, 750 Republican St, Seattle, WA 98109, USA.
Elizabeth Maleche-ObimboDepartment of Paediatrics and Child Health, University of Nairobi, Kenyatta National Hospital, PO Box 20723-00202, Nairobi, Kenya.
Lisa M CranmerDepartment of Pediatrics, Emory University and Children's Healthcare of Atlanta, 100 Woodruff Circle, Atlanta, GA 30322, USA.
Daniel MatemoKenyatta National Hospital, PO Box 20723-00202, Nairobi, Kenya.
Jerphason MechaKenyatta National Hospital, PO Box 20723-00202, Nairobi, Kenya.
John KinuthiaKenyatta National Hospital, PO Box 20723-00202, Nairobi, Kenya.
Sylvia M LaCourseDepartment of Medicine, University of Washington, 750 Republican St, Seattle, WA 98109, USA; Department of Global Health, University of Washington, 325 9th Ave, Seattle, WA, 98104, USA.
Grace C John-StewartDepartment of Medicine, University of Washington, 750 Republican St, Seattle, WA 98109, USA; Department of Pediatrics, University of Washington, 4800 Sand Point Way NE, Seattle, WA 98105, USA; Department of Global Health, University of Washington, 325 9th Ave, Seattle, WA, 98104, USA.
Thomas R HawnDepartment of Medicine, University of Washington, 750 Republican St, Seattle, WA 98109, USA.
University of Washington · USKenyatta National Hospital · KEEmory University · USUniversity of Nairobi · KE

Funding

University of Washington/Fred Hutch Center for AIDS ResearchP30AI027757 · NIAID · UNIVERSITY OF WASHINGTON · PI EDWIN ROBERTO ORELLANA · 1988 to 2026
$104.9M
Pediatric Scientist Development Program (PSDP) [K12]K12HD000850 · NICHD · YALE UNIVERSITY · PI Sallie R. Permar · 1987 to 2026
$44.1M
The role of antibodies in infant TB preventionK23AI143479 · NIAID · EMORY UNIVERSITY · PI CRANMER, LISA M · 2019 to 2023
$950k
Immunoproteomic mechanisms of human macrophage resistance to Mycobacterium tuberculosis infectionK08AI163381 · NIAID · UNIVERSITY OF WASHINGTON · PI ANTERASIAN, CHRISTINE M · 2021 to 2025
$815k
NIAID NIH HHS K08 AI163381NIAID NIH HHS K23 AI143479NIAID NIH HHS P30 AI027757NICHD NIH HHS K12 HD000850
6 · The paper itself

Abstract

backgroundThe immunologic correlates of risk of Mycobacterium tuberculosis (Mtb) infection after BCG vaccination are unknown. The mechanism by which BCG influences the tuberculin skin test (TST) remains poorly understood. We evaluated CD4+ T-cell responses in infants exposed to HIV and uninfected (HEU) who received BCG at birth and examined their role in susceptibility to Mtb infection and influence on TST induration.

methodsHEU infants were enrolled in a randomised clinical trial of isoniazid (INH) to prevent Mtb infection in Kenya. We measured mycobacterial antigen-specific Th1 and Th17 cytokine responses at 6-10 weeks of age prior to INH randomisation and compared responses between Mtb infected and uninfected infants. Outcomes at 14 months of age included TST, QuantiFERON-Plus (QFT-Plus), and ESAT-6/CFP-10-specific non-IFN-γ cytokines measured in QFT-Plus supernatants.

findingsA monofunctional mycobacterial antigen-specific TNF+ CD4+ effector memory (CCR7-CD45RA-) T-cell response at 6-10 weeks of age was associated with Mtb infection at 14 months of age as measured by ESAT-6/CFP-10-specific IFN-γ and non-IFN-γ responses (Odds Ratio 2.26; Confidence Interval 1.27-4.15; P = 0.006). Mycobacterial antigen-specific polyfunctional effector memory Th1 responses at 6-10 weeks positively correlated with TST induration in infants without evidence of Mtb infection at 14 months, an association which was diminished by INH therapy.

interpretationInduction of monofunctional TNF+ CD4+ effector memory T-cell responses may be detrimental in TB vaccine development. This study also provides mechanistic insight into the association of BCG-induced immune responses with TST induration and further evidence that TST-based diagnoses of Mtb infection in infants are imprecise.

fundingThrasher Research Fund.

Indexed as

BCG VaccineCD4-Positive T-LymphocytesHIV InfectionsMemory T CellsMycobacterium tuberculosisTuberculosisAntitubercular AgentsCytokinesHumansInfantInfant, NewbornIsoniazidTumor Necrosis Factor-alphaAntitubercular AgentsBCG VaccineCytokinesIsoniazidTumor Necrosis Factor-alphaBCGHIVT-LymphocytesTuberculin testTuberculosis

Identifiers

PMID35533496
PMCPMC9092381
OpenAlexW4229003361

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.