Evidence map›Paper›PMID 19012957›Full record

ArticleLancet (London, England)2008

HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case-cohort analysis.

M Juliana McElrath, Stephen C De Rosa, Zoe Moodie, Sheri Dubey, Lisa Kierstead, Holly Janes, Olivier D Defawe, Donald K Carter, John Hural, Rama Akondy and 8 more

2 registry-linked trialsOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Lancet (London, England), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 428 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
428citing papers in PubMed, 2 pooled it
27.7field-weighted citation impact, top 1% 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.

NCT01109342 completednot on this mapstarted 2010, after this paper: background citation

Extended Follow-Up for Participants in VRC HIV-1 Recombinant Adenovirus-5 Vector Vaccine Studies in Uganda

TypeobservationalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2010 to 2012ConditionsHIV Infections
NCT01159990 phase1completednot on this mapstarted 2011, after this paper: background citation

A Randomized, Double Blind Phase 1b Trial to Examine the Influence of Antigenic Competition on the Immunogenicity of HIV-1 Gag/Pol: A Comparison of rAd5 Gag/Pol Env A/B/C to rAd5 Gag/Pol

TypeinterventionalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2011 to 2017Enrolled100ConditionsHIV InfectionsArmsrAd5 Gag-Pol Env A/B/C, rAd5 Gag-Pol
3 · Its place in the literature

Who cites it

428 citing papers in PubMed, 2 syntheses or guidelines pooled it, 699 citations in OpenAlex.

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  6. Antigenic competition in CD4Science translational medicine · 2019
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368 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 6 institutions in 1 country.

M Juliana McElrathVaccine and Infectious Disease Institute and the HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Medicine, The University of Washington, Seattle, WA, USA; Department of Laboratory Medicine, The University of Washington, Seattle, WA, USA. Electronic address: jmcelrat@fhcrc.org.
Stephen C De RosaVaccine and Infectious Disease Institute and the HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Laboratory Medicine, The University of Washington, Seattle, WA, USA.
Zoe MoodieVaccine and Infectious Disease Institute and the HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Sheri DubeyMerck Research Laboratories, West Point, PA, USA.
Lisa KiersteadMerck Research Laboratories, West Point, PA, USA.
Holly JanesVaccine and Infectious Disease Institute and the HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Olivier D DefaweVaccine and Infectious Disease Institute and the HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Donald K CarterVaccine and Infectious Disease Institute and the HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
John HuralVaccine and Infectious Disease Institute and the HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Rama AkondyEmory Vaccine Center, Emory University, Atlanta, GA, USA.
Susan P BuchbinderHIV Research Section, San Francisco Department of Public Health, San Francisco, CA, USA.
Michael N RobertsonMerck Research Laboratories, West Point, PA, USA.
Devan V MehrotraMerck Research Laboratories, West Point, PA, USA.
Steven G SelfVaccine and Infectious Disease Institute and the HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Biostatistics, The University of Washington, Seattle, WA, USA.
Lawrence CoreyVaccine and Infectious Disease Institute and the HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Medicine, The University of Washington, Seattle, WA, USA; Department of Laboratory Medicine, The University of Washington, Seattle, WA, USA.
John W ShiverMerck Research Laboratories, West Point, PA, USA.
Danilo R CasimiroMerck Research Laboratories, West Point, PA, USA.
Step Study Protocol Team
United States Military Academy · USFred Hutch Cancer Center · USInfectious Disease Research Institute · USEmory University · USSan Francisco Department of Public Health · USUniversity of Washington · US

Funding

Leadership Group for a Global HIV Vaccine Clinical Trials NetworkU01AI068614 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI COREY, LAWRENCE · 2006 to 2010
$181.5M
University of Washington/Fred Hutch Center for AIDS ResearchP30AI027757 · NIAID · UNIVERSITY OF WASHINGTON · PI Kenneth Sherr · 1988 to 2026
$104.9M
HVTN Laboratory ProgramU01AI068618 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI MCELRATH, MARGARET JULIANA · 2006 to 2010
$82.6M
Atlanta Clinical and Translational Science Institute (ACTSI) RenewalUL1TR000454 · NCATS · EMORY UNIVERSITY · PI STEPHENS, DAVID S · 2012 to 2016
$25.8M
NCATS NIH HHS UL1 TR000454NIAID NIH HHS P30 AI027757NIAID NIH HHS U01 AI068614NIAID NIH HHS U01 AI068618
6 · The paper itself

Abstract

backgroundIn the Step Study, the MRKAd5 HIV-1 gag/pol/nef vaccine did not reduce plasma viraemia after infection, and HIV-1 incidence was higher in vaccine-treated than in placebo-treated men with pre-existing adenovirus serotype 5 (Ad5) immunity. We assessed vaccine-induced immunity and its potential contributions to infection risk.

methodsTo assess immunogenicity, we characterised HIV-specific T cells ex vivo with validated interferon-gamma ELISPOT and intracellular cytokine staining assays, using a case-cohort design. To establish effects of vaccine and pre-existing Ad5 immunity on infection risk, we undertook flow cytometric studies to measure Ad5-specific T cells and circulating activated (Ki-67+/BcL-2(lo)) CD4+ T cells expressing CCR5.

findingsWe detected interferon-gamma-secreting HIV-specific T cells (range 163/10(6) to 686/10(6) peripheral blood mononuclear cells) ex vivo by ELISPOT in 77% (258/354) of people receiving vaccine; 218 of 354 (62%) recognised two to three HIV proteins. We identified HIV-specific CD4+ T cells by intracellular cytokine staining in 58 of 142 (41%) people. In those with reactive CD4+ T cells, the median percentage of CD4+ T cells expressing interleukin 2 was 88%, and the median co-expression of interferon gamma or tumor necrosis factor alpha (TNFalpha), or both, was 72%. We noted HIV-specific CD8+ T cells (range 0.4-1.0%) in 117 of 160 (73%) participants, expressing predominantly either interferon gamma alone or with TNFalpha. Vaccine-induced HIV-specific immunity, including response rate, magnitude, and cytokine profile, did not differ between vaccinated male cases (before infection) and non-cases. Ad5-specific T cells were lower in cases than in non-cases in several subgroup analyses. The percentage of circulating Ki-67+BcL-2(lo)/CCR5+CD4+ T cells did not differ between cases and non-cases.

interpretationConsistent with previous trials, the MRKAd5 HIV-1 gag/pol/nef vaccine was highly immunogenic for inducing HIV-specific CD8+ T cells. Our findings suggest that future candidate vaccines have to elicit responses that either exceed in magnitude or differ in breadth or function from those recorded in this trial.

Indexed as

AIDS VaccinesFemaleHIV-1HIV AntigensHIV InfectionsHumansImmunity, CellularMaleMulticenter Studies as TopicRandomized Controlled Trials as TopicT-LymphocytesAIDS VaccinesHIV Antigens

Identifiers

PMID19012957
PMCPMC2774110
OpenAlexW2162891851

What OpenQuestion holds

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Registered trials

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.