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 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.

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.

scholarly journals Cytotoxic T-Lymphocyte Antigen 4 Gene and Recovery from Hepatitis B Virus Infection

2004 ◽  
Vol 78 (20) ◽  
pp. 11258-11262 ◽  
Author(s):  
Chloe L. Thio ◽  
Timothy L. Mosbruger ◽  
Richard A. Kaslow ◽  
Christopher L. Karp ◽  
Steffanie A. Strathdee ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
T Lymphocyte ◽  
Cell Response ◽  
Cytotoxic T Lymphocyte ◽  
Viral Persistence ◽  
T Cell Response ◽  
Hbv Infection ◽  
B Virus

ABSTRACT Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is an inhibitory T-cell receptor expressed by activated and regulatory T cells. We hypothesized that single-nucleotide polymorphisms (SNPs) in the gene encoding CTLA-4 may affect the vigor of the T-cell response to hepatitis B virus (HBV) infection, thus influencing viral persistence. To test this hypothesis, we genotyped six CTLA4 SNPs, from which all frequent haplotypes can be determined, using a large, matched panel of subjects with known HBV outcomes. Haplotypes with these SNPs were constructed for each subject using PHASE software. The haplotype distribution differed between those with viral persistence and those with clearance. Two haplotypes were associated with clearance of HBV infection, which was most likely due to associations with the SNPs −1722C (odds ratio [OR] = 0.60, P = 0.06) and +49G (OR = 0.73, P = 0.02). The wild-type haplotype, which contains an SNP leading to a decreased T-cell response (+6230A), was associated with viral persistence (OR = 1.32, P = 0.04). These data suggest that CTLA4 influences recovery from HBV infection, which is consistent with the emerging role of T regulatory cells in the pathogenesis of disease.

scholarly journals Cellular Immune Responses to BNT162b2 mRNA COVID-19 Vaccine in Patients with Chronic Lymphocytic Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 638-638
Author(s):  
Gilad Itchaki ◽  
Lior Rokach ◽  
Ohad Benjamini ◽  
Osnat Bairey ◽  
Adi Sabag ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Cell Response ◽  
Research Funding ◽  
T Cell Response ◽  
Lymphocytic Leukemia ◽  
Cell Immune Response ◽  
P Value ◽  
Igg Antibodies ◽  
Cellular Immune

Abstract Background: Patients with chronic lymphocytic leukemia (CLL) are known to have a suboptimal immune response of both humoral and cellular arms. Recently, a BNT162b2 mRNA COVID-19 vaccine was introduced with a high efficacy of 95% in immunocompetent individuals. Approximately half of the patients with CLL fail to mount a humoral response to the vaccine, as detected by anti-spike antibodies. Currently, there is no data available regarding T-cell immune responses following the vaccine of these patients. Aim of the study: To investigate T-cell response determined by interferon gamma (IFNγ) secretion in patients with CLL following BNT162b mRNA Covid-19 vaccine, in comparison with serologic response. Methods: CLL patients from 3 medical centers in Israel were included in the study. All patients received two 30-μg doses of BNT162b2 vaccine (Pfizer), administered intramuscularly 3 weeks apart. For evaluation of SARS-CoV-2 Spike-specific T-cell responses, blood samples were stimulated ex-vivo with Spike protein and secreted IFNγ was quantified (ELISA DuoSet, R&D Systems, Minneapolis, Minnesota, USA). T-cell immune response was considered to be positive for values above 25 pg/ml of Spike-specific response. T-cell subpopulations were characterized by flow cytometry (CD3, CD4, CD8). Anti-spike antibody tests were performed using the Architect AdviseDx SARS-CoV-2 IgG II (Abbot, Lake Forest, Illinois, USA). Statistical analysis was performed using Mann-Whitney test for continuous variables while the Wald Chi-square test was used for comparing categorical variables. Results: 83 patients with CLL were tested for T-cell response. Blood samples were collected after a median time of 139 days post administration of the second dose of vaccine (IQ range 134-152). Out of 83 patients, 68 were eligible for the analysis (with positive internal control). Median age of the cohort was 68 years (56-72); and 44 (65%) were males. 19 (28%) patients were treatment-naïve, most of whom were Binet stage A or B. 31 (46%) patients were on therapy: 17 with a BTK-inhibitor, and 13 with a venetoclax-based regimen. 29 (42%) patients were previously treated with anti-CD20, 13 of whom in the 12 months period prior to vaccination. T cell immune response to the vaccine was evident in 22 (32%) patients. CIRS Score&gt;6 and specifically hypertension were statistically significantly associated with a lower T-cell response (univariate analysis, p-value&lt;0.05). Variables that were associated with the development of T-cell response were presence of del(13q), IgM ≥ 40 mg/dL, and IgA ≥ 80 mg/dL (p-value 0.05-0.1). There was no significant difference with regards to age, gender, other CLL-specific prognostic markers, treatment, and T-cell subpopulation distribution according to flow cytometry (Table 1). The presence of T-cell response highly correlated with both the detection of anti-spike IgG antibodies following the second dose (p=0.0239) and at the time of T-cell testing (n=66, p=0.048, Table 2). While 50% of patients who tested positive for anti-spike IgG antibodies also developed positive T-cell response, only 17% of patients who did not develop T-cell response, tested positive for anti-spike antibodies. Importantly, 24% of the patients who tested negative for anti-spike IgG antibodies, developed positive T cell response. Moreover, the level of the T-cell response (log transformed) correlated linearly with (log transformed) anti-spike IgG titer (adjusted r=0.26 and p =0.026 according to Pearson correlation, Figure 1). Conclusion: We show that cellular immune response to the BNT162b2 mRNA COVID-19 vaccine, is blunted in most CLL patients and that there is a correlation between T-cell response and serologic response to the vaccine. These results need to be validated in a larger cohort. Figure 1 Figure 1. Disclosures Itchaki: AbbVie: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Benjamini: Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Tadmor: AbbVie: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding.

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 Comparing Humoral and Cellular Adaptive Immunity during Convalescent Phase of COVID-19 in Hemodialysis Patients and Kidney Transplant Recipients

2021 ◽  
Vol 10 (21) ◽  
pp. 4833
Author(s):  
Dorota Kamińska ◽  
Hanna Augustyniak-Bartosik ◽  
Katarzyna Kościelska-Kasprzak ◽  
Marcelina Żabińska ◽  
Dorota Bartoszek ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Kidney Transplant ◽  
Adaptive Immunity ◽  
Cell Response ◽  
Cellular Response ◽  
T Cell Response ◽  
Interferon Gamma Release Assay ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

Background. It is still unclear whether COVID-19 convalescent kidney transplant recipients (KTR) and hemodialysis (HD) patients can develop anti-SARS-CoV-2 adaptive immunity. The aim was to characterize and compare the immune response to the virus in HD patients and KTR. Methods. The study included 26 HD patients and 54 KTR—both convalescent (14 HD, 25 KTR) and unexposed. The immune response was assessed by determining the anti-SARS-CoV-2 antibodies in serum and specific T cell response via the interferon-gamma release assay (IGRA). Moreover, blood-morphology-derived parameters, immune cell phenotypes, and acute phase reactants were evaluated. Results. KRT and HD convalescents presented similar serum levels of anti-SARS-CoV-2 IgG and IgA. A negative correlation occurred between IgG and time after the infection was observed. There was a strong relationship between the prevalence of anti-SARS-CoV-2 cellular and humoral responses in both groups. Convalescent IGRA response was significantly higher in HD patients compared to KTR. Conclusions. HD patients and KTR develop humoral and cellular responses after COVID-19. The antibodies levels are similar in both groups of patients. SARS-CoV-2-reactive T cell response is stronger in HD patients compared to KTR. The SARS-CoV-2-specific IgG level decreases with time while IgA and a cellular response are maintained. IGRA proved to be a valuable test for the assessment of specific cellular immunity in immunocompromised HD patients and KTR.

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 Hepatitis B virus-triggered PTEN/β-catenin/c-Myc signaling enhances PD-L1 expression to promote immune evasion

2020 ◽  
Vol 318 (1) ◽  
pp. G162-G173 ◽  
Author(s):  
Yishuang Sun ◽  
Mengxue Yu ◽  
Mengmeng Qu ◽  
Yuhong Ma ◽  
Dandan Zheng ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
Immune Evasion ◽  
Cell Response ◽  
T Cell Response ◽  
Hbv Infection ◽  
B Virus

Hepatitis B virus (HBV) exploits multiple strategies to evade host immune surveillance. Programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) signaling plays a critical role in regulating T cell homeostasis. However, it remains largely unknown as to how HBV infection elevates PD-L1 expression in hepatocytes. A mouse model of HBV infection was established by hydrodynamic injection with a vector containing 1.3-fold overlength HBV genome (pHBV1.3) via the tail vein. Coculture experiments with HBV-expressing hepatoma cells and Jurkat T cells were established in vitro. We observed significant decrease in the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and increase in β-catenin/PD-L1 expression in liver tissues from patients with chronic hepatitis B and mice subjected to pHBV1.3 hydrodynamic injection. Mechanistically, decrease in PTEN enhanced β-catenin/c-Myc signaling and PD-L1 expression in HBV-expressing hepatoma cells, which in turn augmented PD-1 expression, lowered IL-2 secretion, and induced T cell apoptosis. However, β-catenin disruption inhibited PTEN-mediated PD-L1 expression, which was accompanied by decreased PD-1 expression, and increased IL-2 production in T cells. Luciferase reporter assays revealed that c-Myc stimulated transcriptional activity of PD-L1. In addition, HBV X protein (HBx) and HBV polymerase (HBp) contributed to PTEN downregulation and β-catenin/PD-L1 upregulation. Strikingly, PTEN overexpression in hepatocytes inhibited β-catenin/PD-L1 signaling and promoted HBV clearance in vivo. Our findings suggest that HBV-triggered PTEN/β-catenin/c-Myc signaling via HBx and HBp enhances PD-L1 expression, leading to inhibition of T cell response, and promotes HBV immune evasion. NEW & NOTEWORTHY This study demonstrates that during HBV infection, HBV can increase PD-L1 expression via PTEN/β-catenin/c-Myc signaling pathway, which in turn inhibits T cell response and ultimately promotes HBV immune evasion. Targeting this signaling pathway is a potential strategy for immunotherapy of chronic hepatitis B.

Failure of hepatitis B vaccination to induce either humoral or cellular immune response after liver transplantation for hepatitis B related cirrhosis

2005 ◽  
Vol 43 (6) ◽  
pp. 1089-1090 ◽  
Author(s):  
Manuela Merli ◽  
Giorgia Nicolini ◽  
Francesco Adolfo Attili ◽  
Daniele Accapezzato ◽  
Vincenzo Barnaba ◽  
...  
Keyword(s):  
Immune Response ◽  
Liver Transplantation ◽  
Hepatitis B ◽  
Cellular Immune Response ◽  
Hepatitis B Vaccination ◽  
Cellular Immune

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.

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