Transient IL-10 receptor blockade can enhance CD8<sup>+</sup>T cell responses to a simian adenovirus-vectored HIV-1 conserved region immunogen

Clutton, Genevieve; Bridgeman, Anne; Reyes-Sandoval, Arturo; Hanke, Tomáš; Dorrell, Lucy

doi:10.1080/21645515.2015.1009809

Cited by 10 publications

(7 citation statements)

References 21 publications

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“… 10 HIVconsv was tested extensively in pre-clinical settings. 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 To date in regimens involving plasmid DNA, simian (chimpanzee) adenovirus (ChAdV-63), and poxvirus-modified vaccinia virus Ankara (MVA), the HIVconsv vaccines have been tested in eight clinical trials, showed promising immunogenicity and in vitro control of replication of four major clades of HIV-1 and, in combination with latency-reverting agent, produced a signal of viremic control during monitored antiretroviral treatment (ART) pause in early treated patients (Fidler et al., 2018, Intern. AIDS Soc., abstract; Mothe et al., 2017, Intern.…”

Section: Introductionmentioning

confidence: 99%

Efficient Induction of T Cells against Conserved HIV-1 Regions by Mosaic Vaccines Delivered as Self-Amplifying mRNA

Moyo

Vogel

Buus

et al. 2019

Molecular Therapy - Methods & Clinical Development

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Focusing T cell responses on the most vulnerable parts of HIV-1, the functionally conserved regions of HIV-1 proteins, is likely a key prerequisite for vaccine success. For a T cell vaccine to efficiently control HIV-1 replication, the vaccine-elicited individual CD8+ T cells and as a population have to display a number of critical traits. If any one of these traits is suboptimal, the vaccine is likely to fail. Fine-tuning of individual protective characteristics of T cells will require iterative stepwise improvements in clinical trials. Although the second-generation tHIVconsvX immunogens direct CD8+ T cells to predominantly protective and conserved epitopes, in the present work, we have used formulated self-amplifying mRNA (saRNA) to deliver tHIVconsvX to the immune system. We demonstrated in BALB/c and outbred mice that regimens employing saRNA vaccines induced broadly specific, plurifunctional CD8+ and CD4+ T cells, which displayed structured memory subpopulations and were maintained at relatively high frequencies over at least 22 weeks post-administration. This is one of the first thorough analyses of mRNA vaccine-elicited T cell responses. The combination of tHIVconsvX immunogens and the highly versatile and easily manufacturable saRNA platform may provide a long-awaited opportunity to define and optimize induction of truly protective CD8+ T cell parameters in human volunteers.

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Section: Introductionmentioning

confidence: 99%

Efficient Induction of T Cells against Conserved HIV-1 Regions by Mosaic Vaccines Delivered as Self-Amplifying mRNA

Moyo

Vogel

Buus

et al. 2019

Molecular Therapy - Methods & Clinical Development

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“…Therefore, blocking IL-10 signaling may contribute to the establishment of adequate immune responses for the treatment of chronic infections [37,49,52]. Blocking IL-10 signaling can also be useful in immunization protocols that aim to induce immune responses against intracellular pathogens [49,53]. IL-10 signaling can be blocked in vitro by the use of IL-10 or IL-10R reactive molecules, including antibodies, oligonucleotide or peptide aptamers, as well as soluble IL-10 receptor [39,41,52,[54][55][56].…”

Section: Discussionmentioning

confidence: 99%

Blocking IL-10 signaling with soluble IL-10 receptor restores specific lymphoproliferative response in dogs with leishmaniasis caused byLeishmania infantum

Oliveira

Santos

Costa

et al. 2020

Preprint

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AbstractrIL-10 plays a major role in restricting exaggerated inflammatory and immune responses, thus preventing tissue damage. However, the restriction of inflammatory and immune responses by IL-10 can also favor the development and/or persistence of chronic infections or neoplasms. Dogs that succumb to leishmaniasis caused by L. infantum (CanL) develop exhaustion of T lymphocytes and are unable to mount appropriate cellular immune responses to control the infection. These animals fail to mount specific lymphoproliferative responses and produce interferon gamma and TNF-alpha that would activate macrophages and promote destruction of intracellular parasites. Blocking IL-10 signaling may contribute to the treatment of CanL. In order to obtain a tool for this blockage, the present work endeavored to identify the canine casIL-10R1 amino acid sequence, generate a recombinant baculovirus chromosome encoding this molecule, which was expressed in insect cells and subsequently purified to obtain rcasIL-10R1. In addition, rcasIL-10R1 was able to bind to homologous IL-10 and block IL-10 signaling pathway, as well as to promote lymphoproliferation in dogs with leishmaniasis caused by L. infantum.

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“…IL-10 inhibition clears chronic viral infection in animal infection models [ 64 – 67 ]. Inhibiting IL-10 at the time of immunization enhances T cell responses induced by peptide [ 63 ], virus like particle [ 37 ], DNA [ 68 ], adenovirus [ 69 ] vaccines. Immunization together with IL-10 inhibition further improves clearance of chronic viral [ 68 ], bacterial [ 70 ] infection and prevent tumour growth [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Investigation the Possibility of Using Peptides with a Helical Repeating Pattern of Hydro-Phobic and Hydrophilic Residues to Inhibit IL-10

Chen

Yang

et al. 2016

PLoS ONE

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Blockade of IL-10 signalling clears chronic viral and bacterial infections. Immunization together with blockade of IL-10 signalling or relatively low level of IL-10 further enhances viral and bacterial clearance. IL-10 functions through binding to interleukin 10 receptor (IL-10R). Here we showed that peptides P1 and P2 with the hydrophobic and hydrophilic pattern of the IL10R-binding helix in IL-10 could bind with either IL-10R1 or IL-10, and inhibit inflammatory signals with long duration and negligible cytotoxicity in vitro. Furthermore, P2 can enhance antigen specific CD8+ T cell responses in mice induced by the vaccine based on a long peptide of protein E7 in a human papillomavirus type 16.

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Transient IL-10 receptor blockade can enhance CD8⁺T cell responses to a simian adenovirus-vectored HIV-1 conserved region immunogen

Cited by 10 publications

References 21 publications

Efficient Induction of T Cells against Conserved HIV-1 Regions by Mosaic Vaccines Delivered as Self-Amplifying mRNA

Efficient Induction of T Cells against Conserved HIV-1 Regions by Mosaic Vaccines Delivered as Self-Amplifying mRNA

Blocking IL-10 signaling with soluble IL-10 receptor restores specific lymphoproliferative response in dogs with leishmaniasis caused byLeishmania infantum

Investigation the Possibility of Using Peptides with a Helical Repeating Pattern of Hydro-Phobic and Hydrophilic Residues to Inhibit IL-10

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Transient IL-10 receptor blockade can enhance CD8+T cell responses to a simian adenovirus-vectored HIV-1 conserved region immunogen

Cited by 10 publications

References 21 publications

Efficient Induction of T Cells against Conserved HIV-1 Regions by Mosaic Vaccines Delivered as Self-Amplifying mRNA

Efficient Induction of T Cells against Conserved HIV-1 Regions by Mosaic Vaccines Delivered as Self-Amplifying mRNA

Blocking IL-10 signaling with soluble IL-10 receptor restores specific lymphoproliferative response in dogs with leishmaniasis caused byLeishmania infantum

Investigation the Possibility of Using Peptides with a Helical Repeating Pattern of Hydro-Phobic and Hydrophilic Residues to Inhibit IL-10

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Transient IL-10 receptor blockade can enhance CD8⁺T cell responses to a simian adenovirus-vectored HIV-1 conserved region immunogen