scholarly journals Antigenic Evolution on a Global Scale Reveals the Potential Natural Selection of Severe Acute Respiratory Syndrome-Coronavirus 2 by Pre-existing Cross-Reactive T-Cell Immunity

2021 ◽  
Vol 12 ◽  
Author(s):  
Chengdong Zhang ◽  
Xuanxuan Jin ◽  
Xianyang Chen ◽  
Li Qiu ◽  
Qibin Leng ◽  
...  
Keyword(s):  
Natural Selection ◽  
T Cell ◽  
Severe Acute Respiratory Syndrome ◽  
Large Scale ◽  
Nonstructural Protein ◽  
Protein Docking ◽  
Host Cells ◽  
Host Immune System ◽  
Cell Immunity ◽  
Community Transmission

The mutation pattern of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has changed constantly during worldwide community transmission of this virus. However, the reasons for the changes in mutation patterns are still unclear. Accordingly, in this study, we present a comprehensive analysis of over 300 million peptides derived from 13,432 SARS-CoV-2 strains harboring 4,420 amino acid mutations to analyze the potential selective pressure of the host immune system and reveal the driver of mutations in circulating SARS-CoV-2 isolates. The results showed that the nonstructural protein ORF1ab and the structural protein Spike were most susceptible to mutations. Furthermore, mutations in cross-reactive T-cell epitopes between SARS-CoV-2 and seasonal human coronavirus may help SARS-CoV-2 to escape cellular immunity under long-term and large-scale community transmission. Additionally, through homology modeling and protein docking, mutations in Spike protein may enhance the ability of SARS-CoV-2 to invade host cells and escape antibody-mediated B-cell immunity. Our research provided insights into the potential mutation patterns of SARS-CoV-2 under natural selection, improved our understanding of the evolution of the virus, and established important guidance for potential vaccine design.

scholarly journals Antigenic evolution on global scale reveals potential natural selection of SARS-CoV-2 by pre-existing cross-reactive T cell immunity

2020 ◽  
Author(s):  
Chengdong Zhang ◽  
Xuanxuan Jin ◽  
Xianyang Chen ◽  
Qibin Leng ◽  
Tianyi Qiu
Keyword(s):  
Large Scale ◽  
Immune Escape ◽  
Global Scale ◽  
Host Cells ◽  
Common Mutation ◽  
Structural Protein ◽  
Cell Immunity ◽  
Community Transmission ◽  
Mutation Pattern ◽  
Potential Vaccine

ABSTRACTThe mutation pattern of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is constantly changing with the places of transmission, but the reason remains to be revealed. Here, we presented the study that comprehensively analyzed the potential selective pressure of immune system restriction, which can drive mutations in circulating SARS-CoV-2 isolates. The results showed that the most common mutation sites of SARS-CoV-2 proteins were located on the non-structural protein ORF1ab and the structural protein Spike. Further analysis revealed mutations in cross-reactive epitopes between SARS-CoV-2 and seasonal coronavirus may help SARS-CoV-2 to escape cellular immunity under the long-term and large-scale community transmission. Meanwhile, the mutations on Spike protein may enhance the ability of SARS-CoV-2 to enter the host cells and escape the recognition of B-cell immunity. This study will increase the understanding of the evolutionary direction and warn about the potential immune escape ability of SARS-CoV-2, which may provide important guidance for the potential vaccine design.

scholarly journals The Dynamics of Innate and Adaptive Immune Response to Sars Cov-2 Infection and Its Limitations in Human Beings

2021 ◽  
pp. 10-25
Author(s):  
Akpanda Etido ◽  
Emmanuel Ifeanyi Obeagu ◽  
Chukwuma J. Okafor ◽  
Udunma Olive Chijioke ◽  
C. C. N. Vincent ◽  
...  
Keyword(s):  
Immune Response ◽  
Severe Acute Respiratory Syndrome ◽  
Interleukin 1 ◽  
Adaptive Immune Response ◽  
Infection Process ◽  
Host Cells ◽  
Human Beings ◽  
Infected People ◽  
Adaptive Immune ◽  
Cell Immunity

This article deals with the dynamics of the innate and adaptive immune response to severe acute respiratory syndrome coronavirus 2 (SARSCoV2) infection. SARSCoV2 is the viral factor that causes the current global coronavirus pandemic disease 2019 (COVID2019). In terms of person-to-person transmission, it is contacted by inhaling the sneeze droplets of infected people. Severe acute respiratory syndrome Coronavirus 2 attacks lung cells first in its binding mechanism because there are many conservative receptor entries, such as angiotensin converting enzyme 2. The presence of this virus in host cells triggers a variety of protective immune responses, resulting in leads to pneumonia and acute respiratory distress syndrome. In the SarsCoV2 infection process, virus replication, immune response, and inflammatory response are dynamic events that can change rapidly; leading to different results, involving the dynamic expression of pro-inflammatory genes, peaking after the lowest point of respiratory function and leading to a cytokine storm, research on the interleukin 1 (IL1) pathway has shown that it is a factor related in severe respiratory diseases. The weakened expression of cytokines associated with mild infections will also delay T cell immunity to SARSCoV2, thereby prolonging the infection time; this indicates that such afebrile (afebrile) infections and undifferentiated COVID19 cases may promote the virus in the community Spread. This review aims to provide a general overview of the dynamics involved in the human immune response to this viral infection. It also includes a brief description of its structure, discovery history and pathogenesis to facilitate the understanding of this article.

scholarly journals Decay-accelerating factor modulates induction of T cell immunity

2005 ◽  
Vol 201 (10) ◽  
pp. 1523-1530 ◽  
Author(s):  
Peter S. Heeger ◽  
Peter N. Lalli ◽  
Feng Lin ◽  
Anna Valujskikh ◽  
Jinbo Liu ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Function ◽  
Alternative Pathway ◽  
T Cell Immunity ◽  
Host Cells ◽  
Decay Accelerating Factor ◽  
Local Alternative ◽  
Cell Immunity ◽  
Pathway Activation

Decay-accelerating factor (Daf) dissociates C3/C5 convertases that assemble on host cells and thereby prevents complement activation on their surfaces. We demonstrate that during primary T cell activation, the absence of Daf on antigen-presenting cells (APCs) and on T cells enhances T cell proliferation and augments the induced frequency of effector cells. The effect is factor D- and, at least in part, C5-dependent, indicating that local alternative pathway activation is essential. We show that cognate T cell–APC interactions are accompanied by rapid production of alternative pathway components and down-regulation of Daf expression. The findings argue that local alternative pathway activation and surface Daf protein function respectively as a costimulator and a negative modulator of T cell immunity and explain previously reported observations linking complement to T cell function. The results could have broad therapeutic implications for disorders in which T cell immunity is important.

scholarly journals Protective Roles of Folic Acid in the Responses of Bovine Mammary Epithelial Cells to Different Virulent Staphylococcus aureus Strains

Biology ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1164
Author(s):  
Siyuan Mi ◽  
Yongjie Tang ◽  
Liangyu Shi ◽  
Xueqin Liu ◽  
Jingfang Si ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Folic Acid ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Animal Health ◽  
Host Cells ◽  
Host Immune System ◽  
Dna Sensing ◽  
Transcriptional Responses ◽  
Cytoplasmic Dna

Mastitis caused by Staphylococcus aureus (S. aureus) infection is one of the most difficult diseases to treat in dairy cattle. Exploring the biological progression of S. aureus mastitis via the interaction between host, pathogen, and environment is the key to an effective and sustainable improvement of animal health. Here, two strains of S. aureus and a strain of MRSA (Methicillin-resistant Staphylococcus aureus) isolated from cows with different inflammation phenotypes were used to challenge Mac-T cells and to investigate their effects on the global transcriptome of the cells, then to explore the potential regulatory mechanisms of folic acid on S. aureus mastitis prevention. Differential gene expression or splicing analysis showed that different strains of S. aureus led to distinct transcriptional responses from the host immune system. Folic acid could protect host defense against the challenge of S. aureus and MRSA partially through activating cytoplasmic DNA sensing and tight junction pathway. ZBP1 at the upstream of cytoplasmic DNA sensing pathway was verified and related to anti-pathogen through RNA interference. Further enrichment analysis using these transcriptome data with cattle large-scale genome-wide association study (GWAS) data confirmed that ZBP1 gene is highly associated with bovine somatic cell score (SCS) trait. Our data shed light on the potential effect of FA through regulating key gene and then protect host cells’ defense against S. aureus and MRSA.

Targeting Therapeutic T Cells to Tumour Niches.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3009-3009
Author(s):  
Ben Carpenter ◽  
Sara Ghorashian ◽  
Emma Nicholson ◽  
James Edward Griffin ◽  
Maryam Ahmadi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Host Cells ◽  
Brdu Incorporation ◽  
Control Vector ◽  
Multiphoton Imaging ◽  
Cell Immunity

Abstract Abstract 3009 Background: Interactions between tumour cells and host cells within the microenvironment are important in promoting the development of cancer. Tumor niches provide crucial anti-apoptotic and anti-proliferative signals that drive tumor chemoresistance. The CXCR4-CXCL12 chemokine axis forms a critical component of this niche. CXCL12 produced by stromal cells has direct pro-survival effects upon tumor cells, promotes metastasis and recruits CXCR4-expressing regulatory T cell populations that block anti-tumour immunity. In this study, we have tested the hypothesis that targeting therapeutic T cells to CXCR4-dependent niches will improve eradication of tumours in mice. Methods: The murine CXCR4 gene was inserted into retroviral vector, pMP71. Murine T cells were transduced with CXCR4 or control vector and tested for homing in vitro to CXCL12 through chemotaxis assays. In vivo imaging of the putative endosteal bone marrow (BM) niche was performed by multiphoton imaging through cranial frontal bones in osteoblast (collagen 1-α-GFP) reporter mice. In vivo trafficking, competitive transfer and memory recall experiments were performed following transfer of transduced T cells to syngeneic, sub-lethally irradiated mice. Anti-tumour reactivity of CXCR4-transduced T cells was tested in models of allogeneic BM transplantation (BMT). Results: CXCR4-transduced T cells demonstrated enhanced migration towards CXCL12 in vitro. No differences in viability, phenotype or function were observed in CXCR4-transduced versus control T cells in the presence or absence of CXCL12. In competitive assays, CXCR4-transduced CD8 T cells demonstrated a 2-fold greater capacity than controls to home to the BM by 24h after transfer to sub-lethally-irradiated recipients. Multiphoton imaging through cranial frontal bones indicated that fluorescently labelled CXCR4-transduced T cells were closer than control cells to the endosteum (13 μm versus 17 μm, p<0.01). By 14 days, the numbers of CXCR4-transduced CD8 T cells in the BM were 15-fold greater than controls. To test immunity to model antigen, CXCR4 or control vector-transduced OT-1 TCR-transgenic CD8 cells were transferred to sub-lethally irradiated mice before challenge with OVA peptide-loaded dendritic cells. Pre-vaccination, CXCR4-transduced OT-1 cells demonstrated greater engraftment than controls in the BM and spleen. Seven days following vaccination, CXCR4 OT-1 cells demonstrated a greater capacity than control cells to generate IFN-γ to OVA-peptide. Four weeks following vaccination, CXCR4-transduced CD8 T cells showed increased frequencies of cells with a CD44highIL-7Rαhigh memory phenotype than controls, with a greater proportion of cells undergoing proliferation as evaluated by BrdU incorporation. To test T cell immunity against a tumor that exploits the CXCR4-CXCL12 axis to recruit regulatory T cells, B6 BM and CXCR4- or control transduced B6 T cells were transferred to irradiated BALB/c recipients given A20 tumor. Tumor growth was delayed to a greater extent following transfer of CXCR4-compared to control-transduced donor T cells. Conclusion: Over-expression of CXCR4 in CD8 T cells potentiates engraftment, initial effector function and generation of memory cells. Disclosures: Stauss: Cell Medica: Scientific Advisor Other.

scholarly journals SARS -CoV-2 T-cell immunity to variants of concern following vaccination

2021 ◽  
Author(s):  
Kathleen M.E. Gallagher ◽  
Mark B. Leick ◽  
Rebecca C. Larson ◽  
Trisha R. Berger ◽  
Katelin Katsis ◽  
...  
Keyword(s):  
T Cell ◽  
Viral Entry ◽  
Cell Response ◽  
T Cell Responses ◽  
T Cell Response ◽  
T Cell Immunity ◽  
Host Cells ◽  
Viral Control ◽  
Cell Responses ◽  
Cell Immunity

Recently, two mRNA vaccines to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become available, but there is also an emergence of SARS-CoV-2 variants with increased transmissibility and virulence. A major concern is whether the available vaccines will be equally effective against these variants. The vaccines are designed to induce an immune response against the SARS-CoV-2 spike protein, which is required for viral entry to host cells. Immunity to SARS-CoV-2 is often evaluated by antibody production, while less is known about the T-cell response. Here we developed, characterized, and implemented two standardized, functional assays to measure T-cell immunity to SARS-CoV-2 in uninfected, convalescent, and vaccinated individuals. We found that vaccinated individuals had robust T-cell responses to the wild type spike and nucleocapsid proteins, even more so than convalescent patients. We also found detectable but diminished T-cell responses to spike variants (B.1.1.7, B.1.351, and B.1.1.248) among vaccinated but otherwise healthy donors. Since decreases in antibody neutralization have also been observed with some variants, investigation into the T-cell response to these variants as an alternative means of viral control is imperative. Standardized measurements of T-cell responses to SARS-CoV-2 are feasible and can be easily adjusted to determine changes in response to variants.

scholarly journals Differential effects of the second SARS-CoV-2 mRNA vaccine dose on T cell immunity in naive and COVID-19 recovered individuals

2021 ◽  
Author(s):  
Carmen Camara ◽  
Daniel Lozano-Ojalvo ◽  
Eduardo Lopez-Granados ◽  
Estela Paz-Artal ◽  
Marjorie Pion ◽  
...  
Keyword(s):  
T Cell ◽  
Severe Acute Respiratory Syndrome ◽  
Cellular Immunity ◽  
Rapid Development ◽  
Vaccine Dose ◽  
T Cell Immunity ◽  
Current Standard ◽  
Standard Regimen ◽  
Humoral And Cellular Immunity ◽  
Cell Immunity

The rapid development and deployment of mRNA-based vaccines against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to the design of accelerated vaccination schedules that have been extremely effective in naive individuals. While a two-dose immunization regimen with the BNT162b2 vaccine has been demonstrated to provide a 95% efficacy in naive individuals, the effects of the second vaccine dose in individuals who have previously recovered from natural SARS-CoV-2 infection has been questioned. Here we characterized SARS-CoV-2 spike-specific humoral and cellular immunity in naive and previously infected individuals during full BNT162b2 vaccination. Our results demonstrate that the second dose increases both the humoral and cellular immunity in naive individuals. On the contrary, the second BNT162b2 vaccine dose results in a reduction of cellular immunity in COVID-19 recovered individuals, which suggests that a second dose, according to the current standard regimen of vaccination, may be not necessary in individuals previously infected with SARS-CoV-2.

scholarly journals T Cell Immunity Evaluation and Immunodominant Epitope T Cell Receptor Identification of Severe Acute Respiratory Syndrome Coronavirus 2 Spike Glycoprotein in COVID-19 Convalescent Patients

2021 ◽  
Vol 9 ◽  
Author(s):  
Luo Li ◽  
Qian Chen ◽  
Xiaojian Han ◽  
Meiying Shen ◽  
Chao Hu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Severe Acute Respiratory Syndrome ◽  
Vaccine Development ◽  
Cell Receptor ◽  
T Cell Response ◽  
Cell Immunity ◽  
Ifn Γ

A better understanding of the role of T cells in the immune response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is helpful not only for vaccine development but also for the treatment of COVID-19 patients. In this study, we determined the existence of SARS-CoV-2-specific T cells in the blood of COVID-19 convalescents. Meanwhile, the specific T cell response in the non-RBD region was stronger than in the RBD region. We also found that SARS-CoV-2 S-specific reactive CD4+ T cells exhibited higher frequency than CD8+ T cells in recovered COVID-19 patients, with greater number of corresponding epitopes presented. Importantly, we isolated the SARS-CoV-2-specific CD4+ T cell receptors (TCRs) and inserted the TCRs into allogenic CD4+ T cells. These TCR-T cells can be activated by SARS-CoV-2 spike peptide and produce IFN-γ in vitro. These results might provide valuable information for the development of vaccines and new therapies against COVID-19.

scholarly journals Adaptive immunity to SARS-CoV-2

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Daniel M Altmann
Keyword(s):  
T Cell ◽  
Large Scale ◽  
Time Course ◽  
Acute Infection ◽  
Neutralizing Antibody ◽  
Cross Reactivity ◽  
Immune Memory ◽  
Symptomatic Disease ◽  
Cell Immunity ◽  
Human Coronaviruses

Abstract The majority of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 exposed individuals mount an antibody response within around 2-weeks and spike antigen-binding responses correlate well with functional virus neutralization. A minority makes little detectable antibody, generally those with either very mild/asymptomatic disease or those with severe/lethal infection. However, in general, antibody titre correlates with viral load and duration of exposure. There is evidence for cross-reactivity with the other human coronaviruses, though the functional impact of this is as yet unclear. Therapeutic use of neutralizing monoclonal antibodies offers potential for clinical use. While there is evidence for neutralizing antibody as a correlate of protection, some cases indicate the potential for full recovery in the absence of antibody. Studies of T-cell immunity following acute infection show CD4 and CD8 responses to epitopes across diverse viral antigens, possible cross-reactivity with epitopes from the common cold human coronaviruses and large-scale activation. However, in severe cases, there is evidence for T-cell lymphopaenia as well as expression of exhaustion markers. Analysis of serum biomarkers of disease severity implicates a hyperinflammatory contribution to pathogenesis, though this has not been mechanistically delineated beyond a likely role of raised IL-6, considered a therapeutic target. Despite rapid progress, there remain pressing unknowns. It seems likely that immune memory to SARS-CoV-2 may be relatively short lived, but this will need longitudinal investigation. Also, this is a disease of highly variable presentation and time course, with some progressing to protracted, chronic symptoms, which are not understood. The contribution of immunopathological mechanisms to tissue damage, whether in the lung, kidney, heart or blood vessels, is unclear. The immunology underlying the differential susceptibility between the very young and the very old is unresolved, a question with ramifications for vaccine roll-out. The greatest challenge relates to rapid generation, testing and manufacture of vaccines that are immunogenic, protective (at least from symptomatic disease) and safe—a challenge that looks achievable.

scholarly journals Generation of Trypanosoma cruzi-Specific CD8+ T-Cell Immunity Is Unaffected by the Absence of Type I Interferon Signaling

2010 ◽  
Vol 78 (7) ◽  
pp. 3154-3159 ◽  
Author(s):  
Diana L. Martin ◽  
Kaja Murali-Krishna ◽  
Rick L. Tarleton
Keyword(s):  
T Cells ◽  
T Cell ◽  
Trypanosoma Cruzi ◽  
Critical Role ◽  
T Cell Responses ◽  
Host Cells ◽  
Type I Interferons ◽  
Type I ◽  
Cell Responses ◽  
Cell Immunity

ABSTRACT Trypanosoma cruzi is a protozoan parasite that causes human Chagas’ disease, a leading source of congestive heart failure in Central and South America. CD8+ T cells are critical for control of T. cruzi infection, and CD8+ T cells recognizing the immunodominant trans-sialidase gene-encoded peptide TSKB20 (ANYKFTLV) account for approximately 30% of the total CD8+ T-cell population at the peak of infection in C57BL/6 mice. Type I interferons (IFN-I) are pleiotropic cytokines that play a critical role in both innate and adaptive immunity against a variety of infections, but their induction and their role in infection are dictated by the infectious agent. Because type I IFNs and IFN-responsive genes are evident early after T. cruzi infection of host cells, we examined the influence of IFN-I on the development of CD8+ T-cell responses during this infection. Mice lacking the receptor for IFN-I (IFNARKO) and their wild-type counterparts both developed chronic infections and generated similar frequencies of immunodominant TSKB20- and subdominant TSKB18-specific CD8+ T cells following T. cruzi infection. In contrast, peak TSKB20-specific CD8+ T-cell responses generated during infection with vaccinia virus engineered to express TSKB20 were approximately 2.5-fold lower in IFNARKO mice than B6 mice, although after viral clearance, the frequencies of TSKB20-specific CD8+ T cells stabilized at similar levels. Together, these data suggest that IFN-I induction and biology are dependent upon the microbial context and emphasize the need to investigate various infection models for a full understanding of CD8+ T-cell development.

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