Evidence map›Paper›PMID 27192151›Full record

ArticlePloS one2016

Boosting with Subtype C CN54rgp140 Protein Adjuvanted with Glucopyranosyl Lipid Adjuvant after Priming with HIV-DNA and HIV-MVA Is Safe and Enhances Immune Responses: A Phase I Trial.

Agricola Joachim, Asli Bauer, Sarah Joseph, Christof Geldmacher, Patricia J Munseri, Said Aboud, Marco Missanga, Philipp Mann, Britta Wahren, Guido Ferrari and 13 more

Open access · goldAbstract readClinical Trial, Phase I
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
2.0field-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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 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

23 authors at 11 institutions in 5 countries.

Agricola JoachimDepartment of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.ORCID 0000-0001-6639-5293
Asli BauerNational Institute for Medical Research-Mbeya, Medical Research Center, Mbeya, Tanzania.
Sarah JosephMedical Research Council Clinical Trials Unit, University College London, London, United Kingdom.
Christof GeldmacherDepartment of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), Munich, Germany.
Patricia J MunseriDepartment of Internal Medicine, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
Said AboudDepartment of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
Marco MissangaNational Institute for Medical Research-Mbeya, Medical Research Center, Mbeya, Tanzania.
Philipp MannNational Institute for Medical Research-Mbeya, Medical Research Center, Mbeya, Tanzania.
Britta WahrenDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Guido FerrariDepartment of Surgery and Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America.
Victoria R PolonisThe Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
Merlin L RobbThe Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
Jonathan WeberImperial College London, London, United Kingdom.
Roger TatoudImperial College London, London, United Kingdom.
Leonard MabokoNational Institute for Medical Research-Mbeya, Medical Research Center, Mbeya, Tanzania.
Michael HoelscherNational Institute for Medical Research-Mbeya, Medical Research Center, Mbeya, Tanzania.
Eligius F LyamuyaDepartment of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
Gunnel BiberfeldDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Eric SandströmVenhälsan, Karolinska Insitutet at Södersjukhuset, Stockholm, Sweden.
Arne KroidlNational Institute for Medical Research-Mbeya, Medical Research Center, Mbeya, Tanzania.
Muhammad BakariDepartment of Internal Medicine, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
Charlotta NilssonDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Sheena McCormackMedical Research Council Clinical Trials Unit, University College London, London, United Kingdom.
Muhimbili University of Health and Allied Sciences · TZNational Institute for Medical Research · TZGerman Center for Infection Research · DEImperial College London · GBKarolinska Institutet · SEUniversity College London · GBDuke Medical Center · USHenry M. Jackson Foundation · USPublic Health Agency of Sweden · SEStockholm South General Hospital · SEWalter Reed Army Institute of Research · US

Funding

Social and Behavioral Sciences CoreP30AI064518 · NIAID · DUKE UNIVERSITY · PI GEORGIA Doris TOMARAS · 2005 to 2026
$50.5M
Medical Research Council MC_U122861400Medical Research Council MC_UU_12023/23NIAID NIH HHS P30 AI064518Wellcome TrustWellcome Trust 083844/Z/07/Z
6 · The paper itself

Abstract

backgroundA vaccine against HIV is widely considered the most effective and sustainable way of reducing new infections. We evaluated the safety and impact of boosting with subtype C CN54rgp140 envelope protein adjuvanted in glucopyranosyl lipid adjuvant (GLA-AF) in Tanzanian volunteers previously given three immunizations with HIV-DNA followed by two immunizations with recombinant modified vaccinia virus Ankara (HIV-MVA).

methodsForty volunteers (35 vaccinees and five placebo recipients) were given two CN54rgp140/GLA-AF immunizations 30-71 weeks after the last HIV-MVA vaccination. These immunizations were delivered intramuscularly four weeks apart.

resultsThe vaccine was safe and well tolerated except for one episode of asymptomatic hypoglycaemia that was classified as severe adverse event. Two weeks after the second HIV-MVA vaccination 34 (97%) of the 35 previously vaccinated developed Env-specific binding antibodies, and 79% and 84% displayed IFN-γ ELISpot responses to Gag and Env, respectively. Binding antibodies to subtype C Env (included in HIV-DNA and protein boost), subtype B Env (included only in HIV-DNA) and CRF01_AE Env (included only in HIV-MVA) were significantly boosted by the CN54rgp140/GLA-AF immunizations. Functional antibodies detected using an infectious molecular clone virus/peripheral blood mononuclear cell neutralization assay, a pseudovirus/TZM-bl neutralization assay or by assays for antibody-dependent cellular cytotoxicity (ADCC) were not significantly boosted. In contrast, T-cell proliferative responses to subtype B MN antigen and IFN-γ ELISpot responses to Env peptides were significantly enhanced. Four volunteers not primed with HIV-DNA and HIV-MVA before the CN54rgp140/GLA-AF immunizations mounted an antibody response, while cell-mediated responses were rare. After the two Env subtype C protein immunizations, a trend towards higher median subtype C Env binding antibody titers was found in vaccinees who had received HIV-DNA and HIV-MVA prior to the two Env protein immunizations as compared to unprimed vaccinees (p = 0.07).

conclusionWe report excellent tolerability, enhanced binding antibody responses and Env-specific cell-mediated immune responses but no ADCC antibody increase after two immunizations with a subtype C rgp140 protein adjuvanted in GLA-AF in healthy volunteers previously immunized with HIV-DNA and HIV-MVA.

trial registrationInternational Clinical Trials Registry PACTR2010050002122368.

Indexed as

Adjuvants, ImmunologicGlucosidesImmunization, SecondaryLipid AViral VaccinesAdolescentAdultAIDS VaccinesAntibodies, NeutralizingAntibody-Dependent Cell Cytotoxicityenv Gene Products, Human Immunodeficiency VirusFemaleHealthy VolunteersHIV-1HIV AntibodiesHIV InfectionsAdjuvants, ImmunologicAIDS VaccinesAntibodies, Neutralizingenv Gene Products, Human Immunodeficiency Virusglucopyranosyl lipid-AGlucosidesgp140 envelope protein, Human immunodeficiency virus 1HIV AntibodiesImmunoglobulin GInterferon-gammaLipid AMVA vaccineVaccines, DNAViral Vaccines

Identifiers

PMID27192151
PMCPMC4871571
OpenAlexW2403012950

What OpenQuestion holds

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Registered trials

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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.