scholarly journals Quantitative Analysis of tpr Gene Expression in Treponema pallidum Isolates: Differences among Isolates and Correlation with T-Cell Responsiveness in Experimental Syphilis

2006 ◽  
Vol 75 (1) ◽  
pp. 104-112 ◽  
Author(s):  
Lorenzo Giacani ◽  
Barbara Molini ◽  
Charmie Godornes ◽  
Lynn Barrett ◽  
Wesley Van Voorhis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
T Cell ◽  
Cellular Immune Response ◽  
Treponema Pallidum ◽  
T Cell Response ◽  
Transcriptional Analysis ◽  
Different Strains ◽  
Time Amplification ◽  
Cellular Immune

ABSTRACT Transcriptional analysis of the tpr genes in Treponema pallidum subsp. pallidum (referred to here as simply T. pallidum) has been limited to date, and yet the expression of members of this gene family is likely relevant to the pathogenesis of syphilis. Recently, immunological studies and semiquantitative mRNA analysis led to the hypothesis of the modulation of tpr gene transcription during infection and suggested that various strains of T. pallidum might differentially express these genes. In this study we developed a real-time amplification assay to quantify the tpr mRNAs with respect to the 47-kDa lipoprotein message and to compare transcript levels among four different strains of T. pallidum. In addition, we analyzed the lymphocyte responsiveness pattern toward the Tpr antigens in late experimental syphilis to identify tpr genes that had been expressed during the course of infection. The T-cell response has been implicated in clearance of treponemes from early lesions, and some of the Tprs were identified as strong targets of the cellular immune response. We show that message for many of the tpr genes can be detected in treponemes harvested at the peak of early infection. Interestingly, tprK seems to be preferentially expressed in almost every strain, and it is uniformly the target of the strongest cellular immune response. These studies demonstrate the differential expression of certain tpr genes among strains of T. pallidum, and further studies are needed to explore the relationship between tpr gene expression and the clinical course of syphilis in infected individuals.

scholarly journals Humoral and Cellular Immune Response to RNA Immunization with Flavivirus Replicons Derived from Tick-Borne Encephalitis Virus

2005 ◽  
Vol 79 (24) ◽  
pp. 15107-15113 ◽  
Author(s):  
Judith H. Aberle ◽  
Stephan W. Aberle ◽  
Regina M. Kofler ◽  
Christian W. Mandl
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Cell Response ◽  
Cellular Immune Response ◽  
T Cell Response ◽  
The Self ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
Cellular Immune ◽  
Rna Vaccine

ABSTRACT A new vaccination principle against flaviviruses, based on a tick-borne encephalitis virus (TBEV) self-replicating noninfectious RNA vaccine that produces subviral particles, has recently been introduced (R. M. Kofler, J. H. Aberle, S. W. Aberle, S. L. Allison, F. X. Heinz, and C. W. Mandl, Proc. Natl. Acad. Sci. USA 7:1951-1956, 2004). In this study, we evaluated the potential of the self-replicating RNA vaccine in mice in comparison to those of live, attenuated vaccines and a formalin-inactivated whole-virus vaccine (ImmunInject). For this purpose, mice were immunized using gene gun-mediated application of the RNA vaccine and tested for CD8+ T-cell responses, long-term duration, neutralizing capacity, and isotype profile of specific antibodies and protection against lethal virus challenge. We demonstrate that the self-replicating RNA vaccine induced a broad-based, humoral and cellular (Th1 and CD8+ T-cell response) immune response comparable to that induced by live vaccines and that it protected mice from challenge. Even a single immunization with 1 μg of the replicon induced a long-lasting antibody response, characterized by high neutralizing antibody titers, which were sustained for at least 1 year. Nevertheless, it was possible to boost this response further by a second injection with the RNA vaccine, even in the presence of a concomitant CD8+ T-cell response. In this way it was possible to induce a balanced humoral and cellular immune response, similar to infection-induced immunity but without the safety hazards of infectious agents. The results also demonstrate the value of TBEV replicon RNA for inducing protective long-lasting antiviral responses.

Complementary Presence of HBV-Specific Humoral and T-Cellular Immune Response Provide the Long-Lasting Immune Protection After Neonatal Immunization

2021 ◽  
Author(s):  
Yunmei Huang ◽  
Yuting Yang ◽  
Tingting Wu ◽  
Zhiyu Li ◽  
Yao Zhao
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Hepatitis B ◽  
Cell Response ◽  
Cellular Immune Response ◽  
Cellular Response ◽  
T Cell Response ◽  
Hbv Infection ◽  
Hepatitis B Vaccination ◽  
Cellular Immune

Abstract Background: Hepatitis B vaccination is the most cost-effective way to prevent HBV infection. Currently, hepatitis B vaccine (HepB) efficacy was usually assessed by anti-HBs level, but there were little comprehensive analyses of humoral and cellular immune response to HepB in children after neonatal immunization. Methods: A total of 145 children with primary hepatitis B immunization history were involved in this study to evaluate the efficacy of HepB. Blood samples were obtained from 80 eligible children before one dose of HepB booster and 41 children post-booster. Children with anti-HBs at a low level (<10mIU/mL and [10,100) mIU/mL) were received one dose of HepB booster after informed consent. Subjects were be measured anti-HBs, HBsAg-specific T cell responses and frequency of B cell subsets before and after booster. Results: Among 80 subjects, 81.36% of children showed both T cell and anti-HBs responses positive at baseline. After one dose of booster, anti-HBs titer (P<0.0001), positive rate of HBsAg-specific T cell response (P=0.0036) and magnitude of SFCs (P=0.0003) increased significantly. Comparing preexisting anti-HBs titer <10mIU/mL with anti-HBs titer [10,100) mIU/mL, anti-HBs response (P=0.0005) and HBsAg-specific T lymphocyte response (P<0.0001) increased significantly. The change tendency of HBV specific humoral response is complementary to T cellular response with age. Conclusion: Protection from primary HBV immunization persists long on account of the complementary presence of HBV-specific humoral and T-cellular immune response. One dose of HepB booster is efficient enough to produce protective anti-HBs and enhance HBsAg-specific T cell response. In the HBV endemic areas, HepB booster immunization is still the most economical and effective way to prevent HBV infection, especially in children without anti-HBs.

scholarly journals Immunosequencing and epitope mapping reveal substantial preservation of the T cell immune response to Omicron generated by SARS-CoV-2 vaccines

2021 ◽  
Author(s):  
Damon H. May ◽  
Benjamin E. R. Rubin ◽  
Sudeb C. Dalai ◽  
Krishna Patel ◽  
Shahin Shafiani ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cellular Immune Response ◽  
Epitope Mapping ◽  
Protective Efficacy ◽  
T Cell Response ◽  
Cell Immune Response ◽  
Cell Immunity ◽  
Cellular Immune

The Omicron SARS-CoV-2 variant contains 34 mutations in the spike gene likely impacting protective efficacy from vaccines. We evaluated the potential impact of these mutations on the cellular immune response. Combining epitope mapping to SARS-CoV-2 vaccines that we have determined from past experiments along with T cell receptor (TCR) repertoire sequencing from thousands of vaccinated or naturally infected individuals, we estimate the abrogation of the cellular immune response in Omicron. Although 20% of CD4+ T cell epitopes are potentially affected, the loss of immunity mediated by CD4+ T cells is estimated to be slightly above 30% as some of the affected epitopes are relatively more immunogenic. For CD8+ T cells, we estimate a loss of approximately 20%. These reductions in T cell immunity are substantially larger than observed in other widely distributed variants. Combined with the expected substantial loss of neutralization from antibodies, the overall protection provided by SARS-CoV-2 vaccines could be impacted adversely. From analysis of prior variants, the efficacy of vaccines against symptomatic infection has been largely maintained and is strongly correlated with the T cell response but not as strongly with the neutralizing antibody response. We expect the remaining 70% to 80% of on-target T cells induced by SARS-CoV-2 vaccination to reduce morbidity and mortality from infection with Omicron.

scholarly journals A glimpse into the diverse cellular immunity against SARS-CoV-2 

2020 ◽  
Author(s):  
Lung-Ji Chang ◽  
Cheng-Wei Chang ◽  
Yuchen Liu ◽  
Cheng Jiao ◽  
Hongwei Liu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Immune Responses ◽  
Cellular Immunity ◽  
Cellular Immune Response ◽  
Critical Role ◽  
T Cell Response ◽  
Viral Antigens ◽  
Cellular Immune

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific cellular immune response may prove to be essential for long-term immune protection against the novel coronavirus disease 2019 (COVID-19). To assess COVID-19-specific immunity in the population, we synthesized selected peptide pools of SARS-CoV-2 structural and functional proteins, including Spike (S), Membrane (M), envelope (E), Nucleocapsid (N) and Protease (P) as target antigens. Survey of the T cell precursur frequencies in healthy individuals specific to these viral antigens demonstrated a diverse cellular immunity, including high, medium, low and no responders. This was further confirmed by in vitro induction of anti-SARS-CoV-2 T cell immune responses using dendritic cell (DC)/T cell coculture, which was consistent with the corresponding T cell precursor frequencies in each individual tested. In general, the combination of all five antigenic pools induced the strongest cellular immune response, and individual donors responded differently to different viral antigens. Importantly, a secondary in vitro booster stimulation of the T cells with the DC-peptides induced increased anti-viral immune responses in all individuals even in the no responders, suggesting that booster immunization in a vaccine scheme may elicit a broad protection in immune naïve population. Our analysis illustrates the critical role of cellular immunity in fighting COVID-19 and the importance of analyzing anti-SARS-CoV-2 T cell response in addition to antibody response in the population.

scholarly journals Cellular immune response to SARS-CoV-2 infection in humans: a systematic review

2020 ◽  
Author(s):  
Madhumita Shrotri ◽  
May C I van Schalkwyk ◽  
Nathan Post ◽  
Danielle Eddy ◽  
Catherine Huntley ◽  
...  
Keyword(s):  
Systematic Review ◽  
Immune Response ◽  
T Cell ◽  
Cellular Immune Response ◽  
Cellular Response ◽  
T Cell Responses ◽  
Population Level ◽  
T Cell Response ◽  
Cell Responses ◽  
Cellular Immune

Introduction Understanding the cellular immune response to SARS-CoV-2 is critical to vaccine development, epidemiological surveillance and control strategies. This systematic review critically evaluates and synthesises the relevant peer-reviewed and pre-print literature published in recent months. Methods For this systematic review, independent keyword-structured literature searches were carried out in MEDLINE, Embase and COVID-19 Primer for studies published from 01/01/2020-26/06/2020. Papers were independently screened by two researchers, with arbitration of disagreements by a third researcher. Data were independently extracted into a pre-designed Excel template and studies critically appraised using a modified version of the MetaQAT tool, with resolution of disagreements by consensus. Findings were narratively synthesised. Results 61 articles were included. Almost all studies used observational designs, were hospital-based, and the majority had important limitations. Symptomatic adult COVID-19 cases consistently show peripheral T cell lymphopenia, which positively correlates with increased disease severity, duration of RNA positivity, and non-survival; while asymptomatic and paediatric cases display preserved counts. People with severe or critical disease generally develop more robust, virus-specific T cell responses. T cell memory and effector function has been demonstrated against multiple viral epitopes, and, cross-reactive T cell responses have been demonstrated in unexposed and uninfected adults, but the significance for protection and susceptibility, respectively, remains unclear. Interpretation A complex pattern of T cell response to SARS-CoV-2 infection has been demonstrated, but inferences regarding population level immunity are hampered by significant methodological limitations and heterogeneity between studies. In contrast to antibody responses, population-level surveillance of the cellular response is unlikely to be feasible in the near term. Focused evaluation in specific sub-groups, including vaccine recipients, should be prioritised.

Humoral and cellular immune response after influenza vaccination in patients with postcancer fatigue and patients with chronic fatigue syndrome.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9070-9070
Author(s):  
Hetty Prinsen ◽  
Jolanda de Vries ◽  
Foekje Stelma ◽  
Sasja Mulder ◽  
Carla Van Herpen ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Chronic Fatigue Syndrome ◽  
Cellular Immune Response ◽  
Foxp3 Expression ◽  
Chronic Fatigue ◽  
Fatigue Syndrome ◽  
Patient Groups ◽  
Postcancer Fatigue ◽  
Cellular Immune

9070 Background: Postcancer fatigue (PCF) is a frequently occurring problem, impairing quality of life. Patients with chronic fatigue syndrome (CFS) also suffer from severe fatigue symptoms. We hypothesized that in fatigued patients (PCF and CFS) alterations in immune response could explain fatigue symptoms. Therefore, we examined whether the humoral and/or cellular immune response after influenza vaccination differed between fatigued patients and non-fatigued individuals and between PCF and CFS patients. Methods: PCF (n=15) and CFS patients (n=22) were vaccinated against influenza. Age and gender matched non-fatigued cancer survivors (n=12) and healthy controls (n=23) were included for comparison. Antibody responses were measured at baseline and at day 21 by a hemagglutination inhibition test. T cell responses were measured at baseline and at day 7 by a lymphocyte proliferation and activation assay. Results: Both patient groups developed seroprotection rates comparable to the accompanying control groups. Functional T cell reactivity was observed in all groups. Proliferation at baseline was significantly lower in fatigued patients compared to non-fatigued individuals. A significant increase in proliferation from baseline to day 7 was observed in fatigued patients, but not in controls. At day 7, proliferation was not significantly different between fatigued patients and non-fatigued individuals. CD4+CD127-FoxP3+ expression was significantly higher in PCF patients compared to non-fatigued cancer survivors. Conclusions: We observed a lower T cell proliferation at baseline in fatigued patients compared to non-fatigued individuals, suggesting a difference in the baseline state of the immune system between fatigued patients and non-fatigued individuals. Furthermore, the difference in CD4+CD127-FoxP3+ expression between PCF and CFS patients suggests subtle differences in immune state between these two fatigued patient groups. However, since humoral and cellular immune responses after vaccination did not differ significantly between fatigued patients and non-fatigued individuals, vaccination of fatigued patients (PCF and CFS) can be effective.

scholarly journals Endogenous Il10 Alleviates the Systemic Antiviral Cellular Immune Response and T Cell–Mediated Immunopathology in Select Organs of Acutely LCMV-Infected Mice

2015 ◽  
Vol 185 (11) ◽  
pp. 3025-3038 ◽  
Author(s):  
Kristin Jakobshagen ◽  
Beate Ward ◽  
Nikola Baschuk ◽  
Sebastian Huss ◽  
Anna Brunn ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Cellular Immune Response ◽  
Cellular Immune

scholarly journals Preserved T-cell Response in anti-CD20 Treated Multiple Sclerosis Patients Following SARS-CoV-2 Vaccination

2021 ◽  
Author(s):  
Simon Faissner ◽  
Neele Heitmann ◽  
Ricarda Rohling ◽  
Ulas Ceylan ◽  
Marielena Bongert ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
T Cell ◽  
B Cell ◽  
T Cell Response ◽  
Th2 Cells ◽  
Multiple Sclerosis Patients ◽  
Cellular Immune ◽  
Cell Repopulation

Abstract The SARS-CoV-2 pandemic has tremendous implications for the management of patients with autoimmune conditions such as multiple sclerosis (MS) under immune therapies targeting CD20+ B cells (aCD20). We here investigated humoral and cellular immune responses, including neutralization against SARS-CoV-2 WT and delta variant and T cell responses of aCD20-treated MS patients following SARS-CoV-2 vaccination compared to healthy controls. aCD20-treated MS patients had lower anti-SARS-CoV-2-Spike titers, which correlated with B-cell repopulation. Sera of aCD20 treated patients had reduced capacity to neutralize WT and delta pseudoviruses in vitro. On the contrary, aCD20 treated patients elicited higher frequencies of CD3+ T cells, Th1 cells, Th2 cells, Tc1 cells and CD8+IFN-γ+IL-2+ cells. In summary, aCD20 treated patients have a reduced humoral immune response, depending on B cell repopulation, in accordance with a shift of cellular immune response to a stronger Th1, Th2 and Tc1 phenotype, suggesting strong cellular protection against SARS-CoV-2.

A randomized phase II study evaluating the optimal sequencing of sipuleucel-T and androgen deprivation therapy (ADT) in biochemically recurrent prostate cancer (BRPC): Immune results.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5016-5016 ◽  
Author(s):  
Emmanuel S. Antonarakis ◽  
Adam S Kibel ◽  
George Adams ◽  
Lawrence Ivan Karsh ◽  
Aymen Elfiky ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Immune Response ◽  
T Cell ◽  
Immune Responses ◽  
T Cell Activation ◽  
Preliminary Data ◽  
Cellular Immune Response ◽  
Cell Activity ◽  
Optimal Sequencing ◽  
Cellular Immune

5016 Background: ADT is a standard treatment for men with BRPC after failure of local therapy, and has immunomodulatory effects. Sipuleucel-T is an autologous cellular immunotherapy approved for asymptomatic/minimally symptomatic metastatic castrate resistant prostate cancer. The STAND trial (NCT01431391) aimed to evaluate optimal sequencing of sipuleucel-T and ADT in men with BRPC at high risk for metastases (ie PSA doubling time ≤12 mo). Methods: Men were randomized (1:1) to Arm 1: sipuleucel-T followed by ADT (2 wks after 3rd infusion); or Arm 2: ADT (3 mo lead in) followed by sipuleucel-T. All men had 3 doses of sipuleucel-T and 12 mo of ADT (45 mg leuprolide SQ at 6 mo intervals). The primary endpoint is cellular immune response (ELISPOT to PA2024 [PAP-GMCSF]). Secondary endpoints are humoral and cytokine responses, product parameters and safety. Results: 68 men were randomized. Preliminary data show higher levels of serum cytokines in Arm 2 vs Arm 1, with a pattern suggesting a mixed TH1/TH2 cellular immune response; elevations were seen in TH1 (IFNγ, IL 12), TH2 (IL 4, 5, 10, 13) and TH17 (IL 17) subsets (all P<.05). The increase in TH1 cytokines was consistent with a trend toward higher PA2024-specific ELISPOT responses 2 wk after the 3rd sipuleucel-T infusion in Arm 2 vs Arm 1 (40.5 vs 12.8 spots; P=.086), suggesting increased T cell activation in Arm 2. Antigen-specific humoral responses were induced in both arms with no differences yet observed between arms. Sipuleucel-T product parameters were roughly equivalent in both arms with APC activation data indicating a robust prime-boost effect. Conclusions: While confirmation is required, these preliminary data suggest that tumor-specific T cell responses and broad based immune responses are augmented when sipuleucel-T is given after rather than before ADT initiation. These data are consistent with preclinical studies showing that ADT enhances T cell activity, and provide preliminary evidence that combining ADT with sipuleucel-T may augment adaptive immunity. Further follow up will determine whether augmented immune responses correlate with clinical parameters (eg PSA recurrence). Clinical trial information: NCT01431391.

scholarly journals Immune Response to COVID-19: Can We Benefit from the SARS-CoV and MERS-CoV Pandemic Experience?

Pathogens ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 739
Author(s):  
Emilia Sinderewicz ◽  
Wioleta Czelejewska ◽  
Katarzyna Jezierska-Wozniak ◽  
Joanna Staszkiewicz-Chodor ◽  
Wojciech Maksymowicz
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Vaccine Development ◽  
T Cell Response ◽  
High Fatality Rate ◽  
Scientific World ◽  
Specific Antibody Production ◽  
Potential Vaccine ◽  
Cellular Immune

The global range and high fatality rate of the newest human coronavirus (HCoV) pandemic has made SARS-CoV-2 the focus of the scientific world. Next-generation sequencing of the viral genome and a phylogenetic analysis have shown the high homology of SARS-CoV-2 to other HCoVs that have led to local epidemics in the past. The experience acquired in SARS and MERS epidemics may prove useful in understanding the SARS-CoV-2 pathomechanism and lead to effective treatment and potential vaccine development. This study summarizes the immune response to SARS-CoV, MERS-CoV, and SARS-CoV-2 and focuses on T cell response, humoral immunity, and complement system activation in different stages of HCoVs infections. The study also presents the quantity and frequency of T cell responses, particularly CD4+ and CD8+; the profile of cytokine production and secretion; and its relation to T cell type, disease severity, and utility in prognostics of the course of SARS, MERS, and COVID-19 outbreaks. The role of interferons in the therapy of these infections is also discussed. Moreover, the kinetics of specific antibody production, the correlation between humoral and cellular immune response and the immunogenicity of the structural HCoVs proteins and their utility in the development of a vaccine against SARS, MERS, and COVID-19 has been updated.

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