Exploratory clinical studies of a synthetic HIV-1 Tat epitope vaccine in asymptomatic treatment-naïve and antiretroviral-controlled HIV-1 infected subjects plus healthy uninfected subjects

Goldstein, Gideon; Chicca, John J

doi:10.4161/hv.19184

Cited by 10 publications

(10 citation statements)

References 31 publications

(38 reference statements)

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“…The safety profile of TUTI-16 remained excellent, as seen in a previous study, 18 fulfilling the primary endpoint of the study. Randomization was achieved as judged by the CD4 cell counts at entry (Fig.…”

Section: Discussionsupporting

confidence: 48%

“…2). TUTI-16-induced anti-Tat epitope antibodies lower free Tat concentrations in vitro 17 and lower HIV plasma RNA levels in asymptomatic treatment naïve HIV subjects at antibody levels below 40 ng/mL, 18 so the high levels of functional anti-Tat antibody levels achieved in the present study, after the single boost (Fig. 3), fulfilled the first secondary endpoint of immunogenicity.…”

Section: Discussionmentioning

confidence: 81%

“…Interestingly, the low incidence of antibodies in the aviremic ART treated subjects at entry contrasted with the 45% incidence of anti-Tat antibodies, ranging from 43-485 ng/ mL, found in treatment-naïve subjects in a previous study. 18 This suggests that circulating Tat in treatment-naïve subjects induces anti-Tat antibodies but that these subside once ART control of HIV viremia and Tat production is established.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

HIV-1 Tat B-cell epitope vaccination was ineffectual in preventing viral rebound after ART cessation

Goldstein

Damiano

Donikyan

et al. 2012

Human Vaccines & Immunotherapeutics

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Section: Discussionsupporting

confidence: 48%

Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

HIV-1 Tat B-cell epitope vaccination was ineffectual in preventing viral rebound after ART cessation

Goldstein

Damiano

Donikyan

et al. 2012

Human Vaccines & Immunotherapeutics

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“…A number of epitope vaccines have been tested on humans in clinical trials [39,40]. Epitope vaccines have many advantages compared to the whole protein antigen, including increased safety, rational engineering of epitopes for increased potency and breadth, and the ability to focus the immune response on conserved epitopes [41].…”

Section: Discussionmentioning

confidence: 99%

Protective Immunity against Trichinella spiralis Infection Induced by a Multi-Epitope Vaccine in a Murine Model

Wei

Yang

et al. 2013

PLoS ONE

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Trichinellosis is one of the most important food-borne parasitic zoonoses throughout the world. Because infected pigs are the major source of human infections, and China is becoming the largest international producer of pork, the development of a transmission-blocking vaccine to prevent swine from being infected is urgently needed for trichinellosis control in China. Our previous studies have demonstrated that specific Trichinella spiralis paramyosin (Ts-Pmy) and Ts-87 antigen could provide protective immunity against T. spiralis infection in immunized mice. Certain protective epitopes of Ts-Pmy and Ts-87 antigen have been identified. To identify more Ts-Pmy protective epitopes, a new monoclonal antibody, termed 8F12, was produced against the N-terminus of Ts-Pmy. This antibody elicited significant protective immunity in mice against T. spiralis infection by passive transfer and was subsequently used to screen a random phage display peptide library to identify recognized epitopes. Seven distinct positive phage clones were identified and their displayed peptides were sequenced. Synthesized epitope peptides conjugated to keyhole limpet hemocyanin were used to immunize mice, four of which exhibited larval reduction (from 18.7% to 26.3%, respectively) in vaccinated mice in comparison to the KLH control. To increase more effective protection, the epitope 8F7 that was found to induce the highest protection in this study was combined with two other previously identified epitopes (YX1 from Ts-Pmy and M7 from Ts-87) to formulate a multi-epitope vaccine. Mice immunized with this multi-epitope vaccine experienced a 35.0% reduction in muscle larvae burden after being challenged with T. spiralis larvae. This protection is significantly higher than that induced by individual-epitope peptides and is associated with high levels of subclasses IgG and IgG1. These results showed that a multi-epitope vaccine induced better protective immunity than an individual epitope and provided a feasible approach for developing a safer and more effective vaccine against trichinellosis.

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“…Several clinical trials have been done to assess therapeutic and preventive Tat-based vaccinations [128,129,130,131,132]. TUTI-16, a synthetic anti-Tat epitope, successfully induced high titer antibodies against Tat variants from all clades and was tested on asymptomatic HIV infected subjects in phase I/IIa clinical trials [133,134]. TUTI-16 significantly reduced viral load at low vaccine doses, but not at higher doses due to activation of cytokines by the adjuvant components.…”

Section: Targets and Strategies: Approaches To Reduce Hiv Transcrimentioning

confidence: 99%

Strategies to Block HIV Transcription: Focus on Small Molecule Tat Inhibitors

Mousseau

Valente

2012

Biology

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After entry into the target cell, the human immunodeficiency virus type I (HIV) integrates into the host genome and becomes a proviral eukaryotic transcriptional unit. Transcriptional regulation of provirus gene expression is critical for HIV replication. Basal transcription from the integrated HIV promoter is very low in the absence of the HIV transactivator of transcription (Tat) protein and is solely dependent on cellular transcription factors. The 5' terminal region (+1 to +59) of all HIV mRNAs forms an identical stem-bulge-loop structure called the Transactivation Responsive (TAR) element. Once Tat is made, it binds to TAR and drastically activates transcription from the HIV LTR promoter. Mutations in either the Tat protein or TAR sequence usually affect HIV replication, indicating a strong requirement for their conservation. The necessity of the Tat-mediated transactivation cascade for robust HIV replication renders Tat one of the most desirable targets for transcriptional therapy against HIV replication. Screening based on inhibition of the Tat-TAR interaction has identified a number of potential compounds, but none of them are currently used as therapeutics, partly because these agents are not easily delivered for an efficient therapy, emphasizing the need for small molecule compounds. Here we will give an overview of the different strategies used to inhibit HIV transcription and review the current repertoire of small molecular weight compounds that target HIV transcription.

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Exploratory clinical studies of a synthetic HIV-1 Tat epitope vaccine in asymptomatic treatment-naïve and antiretroviral-controlled HIV-1 infected subjects plus healthy uninfected subjects

Cited by 10 publications

References 31 publications

HIV-1 Tat B-cell epitope vaccination was ineffectual in preventing viral rebound after ART cessation

HIV-1 Tat B-cell epitope vaccination was ineffectual in preventing viral rebound after ART cessation

Protective Immunity against Trichinella spiralis Infection Induced by a Multi-Epitope Vaccine in a Murine Model

Strategies to Block HIV Transcription: Focus on Small Molecule Tat Inhibitors

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