scholarly journals Failure of BCG Necessitates to the Development of New Novel Vaccine

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Meena S ◽  
◽  
Goutam P ◽  
Meena LS ◽  
◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Vaccine Development ◽  
Adaptive Immune Response ◽  
Outer Part ◽  
T Cell Response ◽  
Mycobacterial Antigen ◽  
Mycobacterium Tuberculosis H37rv ◽  
Sustained Effects ◽  
The One

The only vaccine available for the deadly disease tuberculosis is Bacillus- Calmette-Guerin (BCG), which is an attenuated vaccine of Mycobacterium bovis. Although this vaccine boosts immune response but it is effective only for 10-20 years, after this there is need to develop immunity against Mycobacterium tuberculosis H37Rv (M. tuberculosis). As the vaccine is botched to provide sustained effects and to protect against disseminated forms of Tuberculosis (TB), it needs a component to heighten antigen specific immune reactions when used in combination with particular vaccine antigens that can also modulate the immune responses to an antigen to advance them. Adjuvants are the one such factor that can be used in vaccines to crack such problems. Many vaccines are under clinical trials in which subunit vaccine has taken attention because they are safer and can be standardized. There are many adjuvants which have been tested in combinations with BCG to increase the activity of vaccine. Mycobacterial antigen 85 A, B, C, present at outer part of cell wall and have great potential as therapeutic approach towards tuberculosis. MPT64 increases T-cell response in tuberculosis patients but there are less evidence about the role of this secreted mycobacterial protein in patients. ESAT 6 is effective T cell antigen and also pore forming toxin which is crucial for the virulence of bacterium. ESAT 6 separately or in compound form with its chaperone CFP- 10 form, regulates host immune response. They efficiently modify innate and adaptive immune response. This review provides an insight in the direction of the vaccine development on the basis of pre-existing credentials.

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.

scholarly journals Preferential CD8 rather than CD4 T-cell response to wear particles of polyether-ether-ketone and highly cross-linked polyethylene

RSC Advances ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 1866-1874 ◽  
Author(s):  
Zhe Du ◽  
Shujun Wang ◽  
You Wang
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Cell Response ◽  
Adaptive Immune Response ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Wear Particles ◽  
Adaptive Immune ◽  
Polyether Ether Ketone ◽  
Ether Ketone

Enriching the understanding of the effects of the particles on the adaptive immune response.

scholarly journals Magnitude and Dynamics of the T-Cell Response to SARS-CoV-2 Infection at Both Individual and Population Levels

2020 ◽  
Author(s):  
Thomas M Snyder ◽  
Rachel M Gittelman ◽  
Mark Klinger ◽  
Damon H May ◽  
Edward J Osborne ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Vaccine Development ◽  
Human Leukocyte ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Clinical Diagnostics ◽  
Cell Repertoire

T cells are involved in the early identification and clearance of viral infections and also support the development of antibodies by B cells. This central role for T cells makes them a desirable target for assessing the immune response to SARS-CoV-2 infection. Here, we combined two high-throughput immune profiling methods to create a quantitative picture of the T-cell response to SARS-CoV-2. First, at the individual level, we deeply characterized 3 acutely infected and 58 recovered COVID-19 subjects by experimentally mapping their CD8 T-cell response through antigen stimulation to 545 Human Leukocyte Antigen (HLA) class I presented viral peptides (class II data in a forthcoming study). Then, at the population level, we performed T-cell repertoire sequencing on 1,815 samples (from 1,521 COVID-19 subjects) as well as 3,500 controls to identify shared "public" T-cell receptors (TCRs) associated with SARS-CoV-2 infection from both CD8 and CD4 T cells. Collectively, our data reveal that CD8 T-cell responses are often driven by a few immunodominant, HLA-restricted epitopes. As expected, the T-cell response to SARS-CoV-2 peaks about one to two weeks after infection and is detectable for at least several months after recovery. As an application of these data, we trained a classifier to diagnose SARS-CoV-2 infection based solely on TCR sequencing from blood samples, and observed, at 99.8% specificity, high early sensitivity soon after diagnosis (Day 3-7 = 85.1% [95% CI = 79.9-89.7]; Day 8-14 = 94.8% [90.7-98.4]) as well as lasting sensitivity after recovery (Day 29+/convalescent = 95.4% [92.1-98.3]). These results demonstrate an approach to reliably assess the adaptive immune response both soon after viral antigenic exposure (before antibodies are typically detectable) as well as at later time points. This blood-based molecular approach to characterizing the cellular immune response has applications in clinical diagnostics as well as in vaccine development and monitoring.

scholarly journals Immune Response Induced by Three Mycobacterium bovis BCG Substrains with Diverse Regions of Deletion in a C57BL/6 Mouse Model

2008 ◽  
Vol 15 (5) ◽  
pp. 750-756 ◽  
Author(s):  
S. M. Irwin ◽  
A. Goodyear ◽  
A. Keyser ◽  
R. Christensen ◽  
J. M. Troudt ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Mouse Model ◽  
Immune Responses ◽  
Mycobacterium Bovis ◽  
Adaptive Immune Response ◽  
T Cell Response ◽  
Interleukin 12 ◽  
Bacterial Burden ◽  
Equal Capacity

ABSTRACT This study was performed to examine the adaptive immune response generated by three Mycobacterium bovis bacillus Calmette-Guérin (BCG) substrains to determine if the number of genomic regions of deletion played a significant role in determining the magnitude of the immune response or affected their ability to reduce the bacterial burden following low-dose aerosol challenge with a virulent M. tuberculosis strain. BCG Connaught, Pasteur, and Sweden were chosen as representative substrains, as they possessed many, intermediate, and few regions of deletion, respectively, as a result of changes in the genome in various regions. Mice were vaccinated subcutaneously and were then examined at 14, 21, and 42 days postvaccination. BCG was observed in the spleen, lung, and lymph nodes. BCG Connaught induced a greater pulmonary T-cell response than the other two substrains at day 14 postvaccination, although by 42 days postvaccination activated T-cell levels dropped to the levels observed in control mice for all three substrains. Among the three substrains, BCG Connaught induced significantly greater levels of interleukin-12 in bone marrow-derived macrophage cultures. Mice challenged at days 14, 21, and 42 postvaccination displayed an equal capacity to reduce the bacterial burden in the lungs and spleen. The data provide evidence that although the BCG substrains generated qualitatively and quantitatively different immune responses, they induced similar reductions in the bacterial burden against challenge with a virulent M. tuberculosis strain in the mouse model of tuberculosis. The data raise questions about the assessment of vaccine immune responses and the relationship to a vaccine's ability to reduce the bacterial burden.

scholarly journals Orf Virus-Based Vaccine Vector D1701-V Induces Strong CD8+ T Cell Response against the Transgene but Not against ORFV-Derived Epitopes

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 295 ◽  
Author(s):  
Alena Reguzova ◽  
Michael Ghosh ◽  
Melanie Müller ◽  
Hanns-Joachim Rziha ◽  
Ralf Amann
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Cellular Immunity ◽  
Cell Response ◽  
Vaccine Development ◽  
Viral Vector ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Specific Immune Response ◽  
Orf Virus

The potency of viral vector-based vaccines depends on their ability to induce strong transgene-specific immune response without triggering anti-vector immunity. Previously, Orf virus (ORFV, Parapoxvirus) strain D1701-V was reported as a novel vector mediating protection against viral infections. The short-lived ORFV-specific immune response and the absence of virus neutralizing antibodies enables repeated immunizations and enhancement of humoral immune responses against the inserted antigens. However, only limited information exists about the D1701-V induced cellular immunity. In this study we employed major histocompatibility complex (MHC) ligandomics and immunogenicity analysis to identify ORFV-specific epitopes. Using liquid chromatography-tandem mass spectrometry we detected 36 ORFV-derived MHC I peptides, originating from various proteins. Stimulated splenocytes from ORFV-immunized mice did not exhibit specific CD8+ T cell responses against the tested peptides. In contrast, immunization with ovalbumin-expressing ORFV recombinant elicited strong SIINFEKL-specific CD8+ T lymphocyte response. In conclusion, our data indicate that cellular immunity to the ORFV vector is negligible, while strong CD8+ T cell response is induced against the inserted transgene. These results further emphasize the ORFV strain D1701-V as an attractive vector for vaccine development. Moreover, the presented experiments describe prerequisites for the selection of T cell epitopes exploitable for generation of ORFV-based vaccines by reverse genetics.

scholarly journals Lymph node swelling combined with temporary effector T cell retention aids T cell response in a model of adaptive immunity

2021 ◽  
Vol 18 (185) ◽  
Author(s):  
Sarah C. Johnson ◽  
Jennifer Frattolin ◽  
Lowell T. Edgar ◽  
Mohammad Jafarnejad ◽  
James E. Moore Jr
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Adaptive Immune Response ◽  
T Cell Response ◽  
Negative Effects ◽  
Macro Scale ◽  
Lymph Node Swelling ◽  
Sphingosine 1 Phosphate ◽  
Retention Aids ◽  
The Impact

Swelling of lymph nodes (LNs) is commonly observed during the adaptive immune response, yet the impact on T cell (TC) trafficking and subsequent immune response is not well known. To better understand the effect of macro-scale alterations, we developed an agent-based model of the LN paracortex, describing the TC proliferative response to antigen-presenting dendritic cells alongside inflammation-driven and swelling-induced changes in TC recruitment and egress, while also incorporating regulation of the expression of egress-modulating TC receptor sphingosine-1-phosphate receptor-1. Analysis of the effector TC response under varying swelling conditions showed that swelling consistently aided TC activation. However, subsequent effector CD8 + TC production was reduced in scenarios where swelling occurred too early in the TC proliferative phase or when TC cognate frequency was low due to increased opportunity for TC exit. Temporarily extending retention of newly differentiated effector TCs, mediated by sphingosine-1-phosphate receptor-1 expression, mitigated any negative effects of swelling by allowing facilitation of activation to outweigh increased access to exit areas. These results suggest that targeting temporary effector TC retention and egress associated with swelling offers new ways to modulate effector TC responses in, for example, immuno-suppressed patients and to optimize of vaccine design.

scholarly journals Regulation of peripheral T cell activation by calreticulin

2006 ◽  
Vol 203 (2) ◽  
pp. 461-471 ◽  
Author(s):  
Simona Porcellini ◽  
Elisabetta Traggiai ◽  
Ursula Schenk ◽  
Denise Ferrera ◽  
Michela Matteoli ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Adaptive Immune Response ◽  
T Cell Response ◽  
Mitogen Activated Protein Kinase ◽  
Immunodeficient Mice ◽  
Adaptive Immune ◽  
The Impact

Regulated expression of positive and negative regulatory factors controls the extent and duration of T cell adaptive immune response preserving the organism's integrity. Calreticulin (CRT) is a major Ca2+ buffering chaperone in the lumen of the endoplasmic reticulum. Here we investigated the impact of CRT deficiency on T cell function in immunodeficient mice reconstituted with fetal liver crt−/− hemopoietic progenitors. These chimeric mice displayed severe immunopathological traits, which correlated with a lower threshold of T cell receptor (TCR) activation and exaggerated peripheral T cell response to antigen with enhanced secretion of inflammatory cytokines. In crt−/− T cells TCR stimulation induced pulsatile cytosolic elevations of Ca2+ concentration and protracted accumulation of nuclear factor of activated T cells in the nucleus as well as sustained activation of the mitogen-activated protein kinase pathways. These observations support the hypothesis that CRT-dependent shaping of Ca2+ signaling critically contributes to the modulation of the T cell adaptive immune response.

scholarly journals SARS-CoV-2 Human T cell Epitopes: adaptive immune response against COVID-19.

2021 ◽  
Author(s):  
Alba Grifoni ◽  
John Sidney ◽  
Randi Vita ◽  
Bjoern Peters ◽  
Shane Crotty ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Adaptive Immune Response ◽  
T Cell Epitopes ◽  
Adaptive Immune ◽  
Human T Cell

scholarly journals IMGT® Biocuration and Comparative Analysis of Bos taurus and Ovis aries TRA/TRD Loci

Genes ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 30
Author(s):  
Perrine Pégorier ◽  
Morgane Bertignac ◽  
Viviane Nguefack Ngoune ◽  
Géraldine Folch ◽  
Joumana Jabado-Michaloud ◽  
...  
Keyword(s):  
Immune Response ◽  
Comparative Analysis ◽  
T Cell ◽  
T Cell Receptors ◽  
Bos Taurus ◽  
Homo Sapiens ◽  
Adaptive Immune Response ◽  
Ovis Aries ◽  
Cell Receptors ◽  
Adaptive Immune

The adaptive immune response provides the vertebrate immune system with the ability to recognize and remember specific pathogens to generate immunity, and mount stronger attacks each time the pathogen is encountered. T cell receptors are the antigen receptors of the adaptive immune response expressed by T cells, which specifically recognize processed antigens, presented as peptides by the highly polymorphic major histocompatibility (MH) proteins. T cell receptors (TR) are divided into two groups, αβ and γδ, which express distinct TR containing either α and β, or γ and δ chains, respectively. The TRα locus (TRA) and TRδ locus (TRD) of bovine (Bos taurus) and the sheep (Ovis aries) have recently been described and annotated by IMGT® biocurators. The aim of the present study is to present the results of the biocuration and to compare the genes of the TRA/TRD loci among these ruminant species based on the Homo sapiens repertoire. The comparative analysis shows similarities but also differences, including the fact that these two species have a TRA/TRD locus about three times larger than that of humans and therefore have many more genes which may demonstrate duplications and/or deletions during evolution.

scholarly journals Checkpoint blockade accelerates a novel switch from an NKT-driven TNFα response toward a T cell driven IFN-γ response within the tumor microenvironment

2021 ◽  
Vol 9 (6) ◽  
pp. e002269
Author(s):  
Shota Aoyama ◽  
Ryosuke Nakagawa ◽  
Satoshi Nemoto ◽  
Patricio Perez-Villarroel ◽  
James J Mulé ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Tumor Growth ◽  
Ex Vivo ◽  
T Cell Response ◽  
Effector Function ◽  
Checkpoint Blockade ◽  
Necrosis Factor Alpha ◽  
Ifn Γ

BackgroundThe temporal response to checkpoint blockade (CB) is incompletely understood. Here, we profiled the tumor infiltrating lymphocyte (TIL) landscape in response to combination checkpoint blockade at two distinct timepoints of solid tumor growth.MethodsC57BL/6 mice bearing subcutaneous MC38 tumors were treated with anti-PD-1 and/or anti-CTLA-4 antibodies. At 11 or 21 days, TIL phenotype and effector function were analyzed in excised tumor digests using high parameter flow cytometry. The contributions of major TIL populations toward overall response were then assessed using ex vivo cytotoxicity and in vivo tumor growth assays.ResultsThe distribution and effector function among 37 distinct TIL populations shifted dramatically between early and late MC38 growth. At 11 days, the immune response was dominated by Tumor necrosis factor alpha (TNFα)-producing NKT, representing over half of all TIL. These were accompanied by modest frequencies of natural killer (NK), CD4+, or CD8+ T cells, producing low levels of IFN-γ. At 21 days, NKT populations were reduced to a combined 20% of TIL, giving way to increased NK, CD4+, and CD8+ T cells, with increased IFN-γ production. Treatment with CB accelerated this switch. At day 11, CB reduced NKT to less than 20% of all TIL, downregulated TNFα across NKT and CD4+ T cell populations, increased CD4+ and CD8+ TIL frequencies, and significantly upregulated IFN-γ production. Degranulation was largely associated with NK and NKT TIL. Blockade of H-2kb and/or CD1d during ex vivo cytotoxicity assays revealed NKT has limited direct cytotoxicity against parent MC38. However, forced CD1d overexpression in MC38 cells significantly diminished tumor growth, suggesting NKT TIL exerts indirect control over MC38 growth.ConclusionsDespite an indirect benefit of early NKT activity, CB accelerates a switch from TNFα, NKT-driven immune response toward an IFN-γ driven CD4+/CD8+ T cell response in MC38 tumors. These results uncover a novel NKT/T cell switch that may be a key feature of CB response in CD1d+ tumors.

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