scholarly journals Early Pro-Inflammatory Signal and T-Cell Activation Associate With Vaccine-Induced Anti-Vaccinia Protective Neutralizing Antibodies

2021 ◽  
Vol 12 ◽  
Author(s):  
Jue Hou ◽  
Shuhui Wang ◽  
Dan Li ◽  
Lindsay N. Carpp ◽  
Tong Zhang ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Neutralizing Antibodies ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Neutralizing Antibody ◽  
Activator Protein 1 ◽  
Successful Vaccine ◽  
Hiv 1 ◽  
Core Genes

Both vaccine “take” and neutralizing antibody (nAb) titer are historical correlates for vaccine-induced protection from smallpox. We analyzed a subset of samples from a phase 2a trial of three DNA/HIV-1 primes and a recombinant Tiantan vaccinia virus-vectored (rTV)/HIV-1 booster and found that a proportion of participants showed no anti-vaccinia nAb response to the rTV/HIV-1 booster, despite successful vaccine “take.” Using a rich transcriptomic and vaccinia-specific immunological dataset with fine kinetic sampling, we investigated the molecular mechanisms underlying nAb response. Blood transcription module analysis revealed the downregulation of the activator protein 1 (AP-1) pathway in responders, but not in non-responders, and the upregulation of T-cell activation in responders. Furthermore, transcriptional factor network reconstruction revealed the upregulation of AP-1 core genes at hour 4 and day 1 post-rTV/HIV-1 vaccination, followed by a downregulation from day 3 until day 28 in responders. In contrast, AP-1 core and pro-inflammatory genes were upregulated on day 7 in non-responders. We speculate that persistent pro-inflammatory signaling early post-rTV/HIV-1 vaccination inhibits the nAb response.

scholarly journals High Titer Persistent Neutralizing Antibodies Induced by TSST-1 Variant Vaccine Against Toxic Shock Cytokine Storm

Toxins ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 640
Author(s):  
Andreas Roetzer ◽  
Norbert Stich ◽  
Nina Model ◽  
Michael Schwameis ◽  
Christa Firbas ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Neutralizing Antibodies ◽  
Cell Activation ◽  
High Titer ◽  
Neutralizing Antibody ◽  
Cytokine Storm ◽  
Toxic Shock ◽  
Antibody Titers ◽  
Toxic Shock Syndrome Toxin

Staphylococcal superantigen toxins lead to a devastating cytokine storm resulting in shock and multi-organ failure. We have previously assessed the safety and immunogenicity of a recombinant toxic shock syndrome toxin 1 variant vaccine (rTSST-1v) in clinical trials (NCT02971670 and NCT02340338). The current study assessed neutralizing antibody titers after repeated vaccination with escalating doses of rTSST-1v. At study entry, 23 out of 34 subjects (67.6%) had neutralizing antibody titers inhibiting T cell activation as determined by 3H-thymidine incorporation at a serum dilution of ≤1:100 with similar figures for inhibition of IL-2 activation (19 of 34 subjects, 55.9%) as assessed by quantitative PCR. After the first vaccination, numbers of subjects with neutralization titers inhibiting T cell activation (61.7% ≥ 1:1000) and inhibiting IL-2 gene induction (88.2% ≥ 1:1000) increased. The immune response was augmented after the second vaccination (inhibiting T cell activation: 78.8% ≥ 1:1000; inhibiting IL-2 induction: 93.9% ≥ 1:1000) corroborated with a third immunization months later in a small subgroup of subjects. Assessment of IFNγ, TNFα and IL-6 inhibition revealed similar results, whereas neutralization titers did not change in placebo participants. Antibody titer studies show that vaccination with rTSST-1v in subjects with no/low neutralizing antibodies can rapidly induce high titer neutralizing antibodies persisting over months.

scholarly journals Gut dendritic cell activation links an altered colonic microbiome to mucosal and systemic T-cell activation in untreated HIV-1 infection

2015 ◽  
Vol 9 (1) ◽  
pp. 24-37 ◽  
Author(s):  
S M Dillon ◽  
E J Lee ◽  
C V Kotter ◽  
G L Austin ◽  
S Gianella ◽  
...  
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Dendritic Cell Activation ◽  
Hiv 1

scholarly journals Factors Associated With CD8+ T-Cell Activation in HIV-1–Infected Patients on Long-term Antiretroviral Therapy

2014 ◽  
Vol 67 (2) ◽  
pp. 153-160 ◽  
Author(s):  
Lu Zheng ◽  
Babafemi Taiwo ◽  
Rajesh T. Gandhi ◽  
Peter W. Hunt ◽  
Ann C. Collier ◽  
...  
Keyword(s):  
T Cell ◽  
Antiretroviral Therapy ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Factors Associated ◽  
Hiv 1

scholarly journals Immunomodulatory Effects of Polysaccharide from Marine FungusPhoma herbarumYS4108 on T Cells and Dendritic Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Song Chen ◽  
Ran Ding ◽  
Yan Zhou ◽  
Xian Zhang ◽  
Rui Zhu ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Interleukin 12 ◽  
Related Factors ◽  
Knock Out ◽  
Specific Immunity

YCP, as a kind of natural polysaccharides from the mycelium of marine filamentous fungusPhoma herbarumYS4108, has great antitumor potentialviaenhancement of host immune response, but little is known about the molecular mechanisms. In the present study, we mainly focused on the effects and mechanisms of YCP on the specific immunity mediated by dendritic cells (DCs) and T cells. T cell /DC activation-related factors including interferon- (IFN-)γ, interleukin-12 (IL-12), and IL-4 were examined with ELISA. Receptor knock-out mice and fluorescence-activated cell sorting are used to analyze the YCP-binding receptor of T cells and DCs. RT-PCR is utilized to measure MAGE-A3 for analyzing the tumor-specific killing effect. In our study, we demonstrated YCP can provide the second signal for T cell activation, proliferation, and IFN-γproduction through binding to toll-like receptor- (TLR-) 2 and TLR-4. YCP could effectively promote IL-12 secretion and expression of markers (CD80, CD86, and MHC II)viaTLR-4 on DCs. Antigen-specific immunity against mouse melanoma cells was strengthened through the activation of T cells and the enhancement of capacity of DCs by YCP. The data supported that YCP can exhibit specific immunomodulatory capacity mediated by T cells and DCs.

scholarly journals A Parameter for IL-10 and TGF-ß Mediated Regulation of HIV-1 Specific T Cell Activation Provides Novel Information and Relates to Progression Markers

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e85604 ◽  
Author(s):  
Andreas Lind ◽  
Kristin Brekke ◽  
Frank Olav Pettersen ◽  
Tom Eirik Mollnes ◽  
Marius Trøseid ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Progression Markers ◽  
Hiv 1

scholarly journals A logical model of HIV-1 interactions with the T-cell activation signalling pathway

2014 ◽  
Vol 31 (7) ◽  
pp. 1075-1083 ◽  
Author(s):  
Oyebode J. Oyeyemi ◽  
Oluwafemi Davies ◽  
David L. Robertson ◽  
Jean-Marc Schwartz
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Signalling Pathway ◽  
Logical Model ◽  
Hiv 1
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