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The therapeutic HIV Env C5/gp41 vaccine candidate Vacc-C5 induces specific T cell regulation in a phase I/II clinical study

Overview of attention for article published in BMC Infectious Diseases, March 2017
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Title
The therapeutic HIV Env C5/gp41 vaccine candidate Vacc-C5 induces specific T cell regulation in a phase I/II clinical study
Published in
BMC Infectious Diseases, March 2017
DOI 10.1186/s12879-017-2316-x
Pubmed ID
Authors

Kristin Brekke, Maja Sommerfelt, Mats Ökvist, Anne Margarita Dyrhol-Riise, Dag Kvale

Abstract

Levels of non-neutralising antibodies (AB) to the C5 domain of HIV Env gp120 are inversely related to progression of HIV infection. In this phase I/II clinical study we investigated safety of Vacc-C5, a peptide-based therapeutic vaccine candidate corresponding to C5/gp41(732-744) as well as the effects on pre-existing AB levels to C5/gp41(732-744), immune activation and T cell responses including exploratory assessments of Vacc-C5-induced T cell regulation. Our hypothesis was that exposure of the C5 peptide motif may have detrimental effects due to several of its HLA-like features and that enhancement of non-neutralising anti-C5 AB by vaccination could reduce C5 exposure and thereby chronic immune activation. Thirty-six HIV patients on effective antiretroviral therapy were randomised to one of three dose levels of Vacc-C5 administered intramuscularly with Alhydrogel or intradermally with GM-CSF as adjuvant through initial immunisation and two booster periods over 26 weeks. Vacc-C5-specific AB were measured by ELISA and T cell responses by both IFN-γ ELISPOT and proliferative assays analysed by flow cytometry. Immune regulation was assessed by functional blockade of the two inhibitory cytokines IL-10 and TGF-β in parallel cultures. Non-parametric statistical tests were applied. Vacc-C5 was found safe and well tolerated in all patients. Only marginal changes in humoral and cellular responses were induced, without any effect on immune activation. Overall, anti-Vacc-C5 AB levels seemed to decrease compared to pre-existing levels. Whereas Vacc-C5-specific CD8(+) T cell proliferative responses increased after the first booster period (p = 0.020; CD4(+), p = 0.057), they were reduced after the second. In contrast, Vacc-C5-induced T cell regulation increased after completed vaccination (p ≤ 0.027) and was lower at baseline in the few AB responders identified (p = 0.027). The therapeutic HIV vaccine candidate Vacc-C5 safely induced only marginal immune responses, whereas Vacc-C5-induced T cell regulation markedly increased. Our data support further attention on immune regulation during therapeutic HIV vaccination studies. NCT01627678 .

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 49 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 49 100%

Demographic breakdown

Readers by professional status Count As %
Other 7 14%
Student > Master 5 10%
Researcher 5 10%
Student > Bachelor 4 8%
Student > Ph. D. Student 4 8%
Other 7 14%
Unknown 17 35%
Readers by discipline Count As %
Medicine and Dentistry 16 33%
Immunology and Microbiology 6 12%
Pharmacology, Toxicology and Pharmaceutical Science 3 6%
Agricultural and Biological Sciences 2 4%
Nursing and Health Professions 2 4%
Other 1 2%
Unknown 19 39%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 May 2017.
All research outputs
#14,807,287
of 23,692,259 outputs
Outputs from BMC Infectious Diseases
#3,907
of 7,895 outputs
Outputs of similar age
#175,397
of 310,398 outputs
Outputs of similar age from BMC Infectious Diseases
#103
of 168 outputs
Altmetric has tracked 23,692,259 research outputs across all sources so far. This one is in the 35th percentile – i.e., 35% of other outputs scored the same or lower than it.
So far Altmetric has tracked 7,895 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.5. This one is in the 47th percentile – i.e., 47% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 310,398 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 168 others from the same source and published within six weeks on either side of this one. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.