Evidence map›Paper›PMID 33104758›Full record

ArticlePLoS pathogens2020

Therapeutic vaccination of SIV-infected, ART-treated infant rhesus macaques using Ad48/MVA in combination with TLR-7 stimulation.

Katherine M Bricker, Veronica Obregon-Perko, Ferzan Uddin, Brianna Williams, Emilie A Uffman, Carolina Garrido, Genevieve G Fouda, Romas Geleziunas, Merlin Robb, Nelson Michael and 2 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 9% 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

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Nonhuman primate models of pediatric viral diseases.Frontiers in cellular and infection microbiology · 2024
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
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  18. HIV Reservoirs: Modeling, Quantification, and Approaches to a Cure.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  19. Article
  20. 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

12 authors at 6 institutions in 1 country.

Katherine M BrickerDepartment of Pediatrics, Emory University School of Medicine, Atlanta, GA, United States of America.ORCID 0000-0003-3339-0175
Veronica Obregon-PerkoDepartment of Pediatrics, Emory University School of Medicine, Atlanta, GA, United States of America.ORCID 0000-0002-6034-1443
Ferzan UddinDepartment of Pediatrics, Emory University School of Medicine, Atlanta, GA, United States of America.
Brianna WilliamsDepartment of Pediatrics, Emory University School of Medicine, Atlanta, GA, United States of America.
Emilie A UffmanDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC, United States of America.ORCID 0000-0002-5902-0028
Carolina GarridoDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC, United States of America.
Genevieve G FoudaDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC, United States of America.ORCID 0000-0002-0960-1019
Romas GeleziunasGilead Sciences, Inc., Foster City, CA, United States of America.
Merlin RobbUS Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States of America.ORCID 0000-0003-3949-9649
Nelson MichaelUS Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States of America.
Dan H BarouchCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States of America.
Ann ChahroudiDepartment of Pediatrics, Emory University School of Medicine, Atlanta, GA, United States of America.ORCID 0000-0001-7479-9546
Emory University · USDuke Medical Center · USWalter Reed Army Institute of Research · USBeth Israel Deaconess Medical Center · USDuke University · USGilead Sciences (United States) · US

Funding

Yerkes National Primate Research Center Role of type-I IFN in regulating COVID-19 induced inflammation and pathogenesisP51OD011132 · OD · EMORY UNIVERSITY · PI Joon Sup Lee · 2012 to 2026
$167.0M
Virology and Molecular Biomarkers CoreP30AI050409 · NIAID · EMORY UNIVERSITY · PI Ann M Chahroudi, Colleen F Kelley · 2002 to 2026
$74.0M
Winship Cancer Institute Cancer Center Support GrantP30CA138292 · NCI · EMORY UNIVERSITY · PI Suresh S Ramalingam · 2009 to 2026
$47.5M
The origin, predictors, and immune correlates of viral rebound in orally SHIV infected infant monkeysP01AI131276 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI PERMAR, SALLIE R. · 2017 to 2021
$8.3M
Immune interventions in SIV-infected ART-suppressed infant macaquesR01AI133706 · NIAID · EMORY UNIVERSITY · PI CHAHROUDI, ANN M · 2017 to 2021
$4.1M
NCI NIH HHS P30 CA138292NIAID NIH HHS P01 AI131276NIAID NIH HHS P30 AI050409NIAID NIH HHS R01 AI133706NIH HHS P51 OD011132
6 · The paper itself

Abstract

Globally, 1.8 million children are living with HIV-1. While antiretroviral therapy (ART) has improved disease outcomes, it does not eliminate the latent HIV-1 reservoir. Interventions to delay or prevent viral rebound in the absence of ART would be highly beneficial for HIV-1-infected children who now must remain on daily ART throughout their lifespan. Here, we evaluated therapeutic Ad48-SIV prime, MVA-SIV boost immunization in combination with the TLR-7 agonist GS-986 in rhesus macaque (RM) infants orally infected with SIVmac251 at 4 weeks of age and treated with a triple ART regimen beginning 4 weeks after infection. We hypothesized immunization would enhance SIV-specific T cell responses during ART-mediated suppression of viremia. Compared to controls, vaccinated infants had greater magnitude SIV-specific T cell responses (mean of 3475 vs 69 IFN-γ spot forming cells (SFC) per 106 PBMCs, respectively, P = 0.01) with enhanced breadth of epitope recognition and increased CD8+ and CD4+ T cell polyfunctionality (P = 0.004 and P = 0.005, respectively). Additionally, SIV-specific gp120 antibodies against challenge and vaccine virus strains were significantly elevated following MVA boost (P = 0.02 and P < 0.001, respectively). GS-986 led to expected immune stimulation demonstrated by activation of monocytes and T cells 24 hours post-dose. Despite the vaccine-induced immune responses, levels of SIV DNA in peripheral and lymph node CD4+ T cells were not significantly different from controls and a similar time to viral rebound and viral load set point were observed following ART interruption in both groups. We demonstrate infant RMs mount a robust immunological response to this immunization, but vaccination alone was not sufficient to impact viral reservoir size or modulate rebound dynamics following ART release. Our findings hold promise for therapeutic vaccination as a part of a combination cure approach in children and highlight the importance of a pediatric model to evaluate HIV-1 cure interventions in this unique setting of immune development.

Indexed as

AdenoviridaeAnimalsAnimals, NewbornCD4-Positive T-LymphocytesFemaleGenetic VectorsMacaca mulattaMaleSAIDS VaccinesSimian Acquired Immunodeficiency SyndromeSimian Immunodeficiency VirusToll-Like Receptor 7VaccinationViral LoadViremiaVirus ReplicationSAIDS VaccinesToll-Like Receptor 7

Identifiers

PMID33104758
PMCPMC7644092
OpenAlexW3093564455

What OpenQuestion holds

Textmetadata
LicenceCC0
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.