MTBVAC: Attenuating the Human Pathogen of Tuberculosis (TB) Toward a Promising Vaccine against the TB Epidemic.

Abstract:

:Bacille Calmette-Guérin (BCG) is a live-attenuated strain of Mycobacterium bovis developed a century ago by repeated subculture. It remains the only vaccine against tuberculosis (TB) in use today, and it offers variable protection against the respiratory forms of TB responsible for transmission. The principal genetic basis for BCG attenuation is the loss of the region of difference 1 (RD1) that includes the genes codifying for production and export of the major virulence factor ESAT6. Today more than 13 TB vaccine candidates are in clinical evaluation. One of these candidates is MTBVAC, which is based on a rationally attenuated Mycobacterium tuberculosis clinical isolate belonging to modern lineage 4, one of the most widespread lineages among humans. MTBVAC conserves most of the T cell epitopes described for TB including the major immunodominant antigens ESAT6 and CFP10 of the RD1, deleted in BCG. After almost 20 years of discovery and preclinical development, MTBVAC is the only live attenuated vaccine based on a human pathogen that has successfully entered clinical trials as a preventive vaccine in newborns, aiming to replace BCG, and as a preventive vaccine in adolescents and adults (BCG-vaccinated at birth). Our recent preclinical studies have demonstrated that MTBVAC-induced immunity to ESAT6 and CFP10 correlate with improved efficacy relative to BCG encouraging exploration of these responses in human clinical trials as potential biomarkers and identification of these antigens as possible correlates of vaccine-induced protection. Such data would be extremely valuable as they would greatly accelerate clinical development to efficacy trials.

journal_name

Front Immunol

journal_title

Frontiers in immunology

authors

Gonzalo-Asensio J,Marinova D,Martin C,Aguilo N

doi

10.3389/fimmu.2017.01803

subject

Has Abstract

pub_date

2017-12-15 00:00:00

pages

1803

issn

1664-3224

journal_volume

8

pub_type

杂志文章,评审
  • MicroRNA-130a Contributes to Type-2 Classical DC-activation in Sjögren's Syndrome by Targeting Mitogen- and Stress-Activated Protein Kinase-1.

    abstract::Objectives: Considering the critical role of microRNAs (miRNAs) in regulation of cell activation, we investigated their role in circulating type-2 conventional dendritic cells (cDC2s) of patients with primary Sjögren's syndrome (pSS) compared to healthy controls (HC). Methods: CD1c-expressing cDC2s were isolated from ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.01335

    authors: Lopes AP,van Roon JAG,Blokland SLM,Wang M,Chouri E,Hartgring SAY,van der Wurff-Jacobs KMG,Kruize AA,Burgering BMT,Rossato M,Radstake TRDJ,Hillen MR

    更新日期:2019-06-20 00:00:00

  • Novel Genome-Editing Tools to Model and Correct Primary Immunodeficiencies.

    abstract::Severe combined immunodeficiency (SCID) and other severe non-SCID primary immunodeficiencies (non-SCID PID) can be treated by allogeneic hematopoietic stem cell (HSC) transplantation, but when histocompatibility leukocyte antigen-matched donors are lacking, this can be a high-risk procedure. Correcting the patient's o...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2015.00250

    authors: Ott de Bruin LM,Volpi S,Musunuru K

    更新日期:2015-05-21 00:00:00

  • The Receptor for Advanced Glycation Endproducts Does Not Contribute to Pathology in a Mouse Mesenteric Ischemia/Reperfusion-Induced Injury Model.

    abstract::The receptor for advanced glycation endproducts (RAGE) can engage a diverse class of ligands and contribute to the immune and inflammatory response to infection and injury. It is known to be a pathogenic receptor in many inflammatory diseases, including ischemia/reperfusion (IR) injuries in several tissues; however, i...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2015.00614

    authors: Wu MC,Gilmour TD,Mantovani S,Woodruff TM

    更新日期:2015-12-07 00:00:00

  • Predictable Irreversible Switching Between Acute and Chronic Inflammation.

    abstract::Many a disease associates with inflammation. Upon binding of antigen-antibody complexes to immunoglobulin-like receptors, mast cells release tumor necrosis factor-α and proteases, causing fibroblasts to release endogenous antigens that may be cross reactive with exogenous antigens. We made a predictive dynamic map of ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.01596

    authors: Abudukelimu A,Barberis M,Redegeld FA,Sahin N,Westerhoff HV

    更新日期:2018-08-07 00:00:00

  • Macrophage-Neisseria gonorrhoeae Interactions: A Better Understanding of Pathogen Mechanisms of Immunomodulation.

    abstract::Neisseria gonorrhoeae is a significant health problem worldwide due to multi-drug resistance issues and absence of an effective vaccine. Patients infected with N. gonorrhoeae have not shown a better immune response in successive infections. This might be explained by the fact that N. gonorrhoeae possesses several mech...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.03044

    authors: Escobar A,Rodas PI,Acuña-Castillo C

    更新日期:2018-12-21 00:00:00

  • Mesenchymal cell differentiation during lymph node organogenesis.

    abstract::Secondary lymphoid tissues such as lymph nodes are essential for the interactions between antigen presenting cells and lymphocytes that result in adaptive immune responses that protect the host against invading pathogens. The specialized architecture of these organs facilitates the cognate interactions between antigen...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2012.00381

    authors: Brendolan A,Caamaño JH

    更新日期:2012-12-14 00:00:00

  • Development of Different Methods for Preparing Acinetobacter baumannii Outer Membrane Vesicles Vaccine: Impact of Preparation Method on Protective Efficacy.

    abstract::Acinetobacter baumannii (A. baumannii) is becoming a common global concern due to the emergence of multi-drug or pan-drug resistant strains. Confronting the issue of antimicrobial resistance by developing vaccines against the resistant pathogen is becoming a common strategy. In this study, different methods for prepar...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.01069

    authors: Li S,Chen DQ,Ji L,Sun S,Jin Z,Jin ZL,Sun HW,Zeng H,Zhang WJ,Lu DS,Luo P,Zhao AN,Luo J,Zou QM,Li HB

    更新日期:2020-06-23 00:00:00

  • Intestinal epithelium and autophagy: partners in gut homeostasis.

    abstract::One of the most significant challenges of cell biology is to understand how each type of cell copes with its specific workload without suffering damage. Among the most intriguing questions concerns intestinal epithelial cells in mammals; these cells act as a barrier between the internally protected region and the exte...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2013.00301

    authors: Randall-Demllo S,Chieppa M,Eri R

    更新日期:2013-09-30 00:00:00

  • Deciphering Natural Killer Cell Homeostasis.

    abstract::Natural killer (NK) cells have a central role within the innate immune system, eliminating virally infected, foreign and transformed cells through their natural cytotoxic capacity. Release of their cytotoxic granules is tightly controlled through the balance of a large repertoire of inhibitory and activating receptors...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.00812

    authors: Pfefferle A,Jacobs B,Haroun-Izquierdo A,Kveberg L,Sohlberg E,Malmberg KJ

    更新日期:2020-05-12 00:00:00

  • Autoimmunity After Ischemic Stroke and Brain Injury.

    abstract::Ischemic Stroke is a major cause of morbidity and mortality worldwide. Sterile inflammation occurs after both stroke subtypes and contributes to neuronal injury and damage to the blood-brain barrier with release of brain antigens and a potential induction of autoimmune responses that escape central and peripheral tole...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.00686

    authors: Javidi E,Magnus T

    更新日期:2019-04-02 00:00:00

  • Cecal CircRNAs Are Associated With the Response to Salmonella Enterica Serovar Enteritidis Inoculation in the Chicken.

    abstract::Circular RNAs (circRNAs) are a class of endogenous noncoding RNA, which is different from linear RNA. CircRNA is an RNA molecule with a closed loop structure formed by reverse splicing. CircRNAs have been studied in several organisms, however, the circRNAs associated with the response to Salmonella enterica serovar En...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.01186

    authors: Zheng L,Liu L,Lin L,Tang H,Fan X,Lin H,Li X

    更新日期:2019-05-31 00:00:00

  • Quantity and Quality of Inhaled Dose Predicts Immunopathology in Tuberculosis.

    abstract::Experimental animal models of tuberculosis (TB) have convincingly demonstrated that inhaled dose predicts immunopathology and survival. In contrast, the importance of inhaled dose has generally not been appreciated in TB epidemiology, clinical science, or the practice of TB control. Infectiousness of TB patients has t...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2015.00313

    authors: Fennelly KP,Jones-López EC

    更新日期:2015-06-29 00:00:00

  • Persistent Immune Activation in CVID and the Role of IVIg in Its Suppression.

    abstract::Common variable immunodeficiency (CVID) is one of the most common and clinically important primary immune deficiencies. CVID patients have poor humoral immunity, resulting in recurrent infections of the gastrointestinal and upper respiratory tracts, as well as increased incidence of some forms of cancers and autoimmun...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2014.00637

    authors: Paquin-Proulx D,Sandberg JK

    更新日期:2014-12-16 00:00:00

  • Elementary steps in T cell receptor triggering.

    abstract::The mechanism by which antigen binding to the T cell antigen receptor (TCR) generates intracellular signaling, a process termed TCR triggering, is incompletely understood. A large body of experimental evidence has implicated multiple biophysical/biochemical effects and multiple molecules in the process of TCR triggeri...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2011.00091

    authors: Dushek O

    更新日期:2012-01-10 00:00:00

  • Human NK Cell Subsets in Pregnancy and Disease: Toward a New Biological Complexity.

    abstract::In humans, NK cells are mainly identified by the surface expression levels of CD56 and CD16, which differentiate between five functionally different NK cell subsets. However, nowadays NK cells are considered as a more heterogeneous population formed by various subsets differing in function, surface phenotype, and anat...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2016.00656

    authors: Cristiani CM,Palella E,Sottile R,Tallerico R,Garofalo C,Carbone E

    更新日期:2016-12-27 00:00:00

  • Activation of the Complement System in the Lower Genital Tract During Pregnancy and Delivery.

    abstract:Background:Human pregnancy alters profoundly the immune system. The local involvement and mechanisms of activation of the complement system in the cervicovaginal milieu during pregnancy and delivery remain unexplored. Objectives:To determine whether normal pregnancy and delivery are associated with local activation of...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.563073

    authors: Livson S,Jarva H,Kalliala I,Lokki AI,Heikkinen-Eloranta J,Nieminen P,Meri S

    更新日期:2021-01-11 00:00:00

  • Mechanisms of Graft-versus-Host Disease Prevention by Post-transplantation Cyclophosphamide: An Evolving Understanding.

    abstract::Post-transplantation cyclophosphamide (PTCy) has been highly successful at preventing severe acute and chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). The clinical application of this approach was based on extensive studies in major histocompatibility complex (MHC)-m...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.02668

    authors: Nunes NS,Kanakry CG

    更新日期:2019-11-29 00:00:00

  • Human Norovirus Proteins: Implications in the Replicative Cycle, Pathogenesis, and the Host Immune Response.

    abstract::Human noroviruses (HuNoVs) are the cause of more than 95% of epidemic non-bacterial gastroenteritis worldwide, with some lethal cases. These viral agents affect people of all ages. However, young children and older adults are the highest-risk groups, being affected with the greatest rate of hospitalizations and morbid...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.00961

    authors: Campillay-Véliz CP,Carvajal JJ,Avellaneda AM,Escobar D,Covián C,Kalergis AM,Lay MK

    更新日期:2020-06-16 00:00:00

  • Mesenchymal stem cells are short-lived and do not migrate beyond the lungs after intravenous infusion.

    abstract::Mesenchymal stem cells (MSC) are under investigation as a therapy for a variety of disorders. Although animal models show long term regenerative and immunomodulatory effects of MSC, the fate of MSC after infusion remains to be elucidated. In the present study the localization and viability of MSC was examined by isola...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2012.00297

    authors: Eggenhofer E,Benseler V,Kroemer A,Popp FC,Geissler EK,Schlitt HJ,Baan CC,Dahlke MH,Hoogduijn MJ

    更新日期:2012-09-26 00:00:00

  • PD-L1/PD-1 Pattern of Expression Within the Bone Marrow Immune Microenvironment in Smoldering Myeloma and Active Multiple Myeloma Patients.

    abstract:Background:The PD-1/PD-L1 axis has recently emerged as an immune checkpoint that controls antitumor immune responses also in hematological malignancies. However, the use of anti-PD-L1/PD-1 antibodies in multiple myeloma (MM) patients still remains debated, at least in part because of discordant literature data on PD-L1...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.613007

    authors: Costa F,Vescovini R,Marchica V,Storti P,Notarfranchi L,Dalla Palma B,Toscani D,Burroughs-Garcia J,Catarozzo MT,Sammarelli G,Giuliani N

    更新日期:2021-01-08 00:00:00

  • Uncovering the Role of RNA-Binding Proteins in Gene Expression in the Immune System.

    abstract::Fighting external pathogens requires an ever-changing immune system that relies on tight regulation of gene expression. Transcriptional control is the first step to build efficient responses while preventing immunodeficiencies and autoimmunity. Post-transcriptional regulation of RNA editing, location, stability, and t...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.01094

    authors: Díaz-Muñoz MD,Turner M

    更新日期:2018-05-23 00:00:00

  • Nanobodies and Nanobody-Based Human Heavy Chain Antibodies As Antitumor Therapeutics.

    abstract::Monoclonal antibodies have revolutionized cancer therapy. However, delivery to tumor cells in vivo is hampered by the large size (150 kDa) of conventional antibodies. The minimal target recognition module of a conventional antibody is composed of two non-covalently associated variable domains (VH and VL). The proper o...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2017.01603

    authors: Bannas P,Hambach J,Koch-Nolte F

    更新日期:2017-11-22 00:00:00

  • What Is the Clinical Relevance of TNF Inhibitor Immunogenicity in the Management of Patients With Rheumatoid Arthritis?

    abstract::Tumor necrosis factor-α inhibitors (TNFis) have revolutionized the management of rheumatoid arthritis (RA), however despite considerable progress, only a small proportion of patients maintain long-term clinical response. Selection of, and switching between, biologics is mainly empirical, experiential, and not evidence...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.00589

    authors: Mehta P,Manson JJ

    更新日期:2020-04-07 00:00:00

  • Immunoglobulin replacement therapy in secondary hypogammaglobulinemia.

    abstract::Immunoglobulin (Ig) replacement therapy dramatically changed the clinical course of primary hypogammaglobulinemias, significantly reducing the incidence of infectious events. Over the last two decades its use has been extended to secondary antibody deficiencies, particularly those related to hematological disorders as...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2014.00626

    authors: Compagno N,Malipiero G,Cinetto F,Agostini C

    更新日期:2014-12-08 00:00:00

  • Enrichment of HLA Types and Single-Nucleotide Polymorphism Associated With Non-progression in a Strictly Defined Cohort of HIV-1 Controllers.

    abstract::HIV-1 controllers (HIC) are extremely rare patients with the ability to control viral replication, maintain unchanging CD4 T-cell count, and evade disease progression for extensive periods of time, in the absence of antiretroviral therapy. In order to establish the representation of key genetic correlates of atypical ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.00746

    authors: Westrop SJ,Cocker ATH,Boasso A,Sullivan AK,Nelson MR,Imami N

    更新日期:2017-06-27 00:00:00

  • Non-Specific Antibodies Induce Lysosomal Activation in Atlantic Salmon Macrophages Infected by Piscirickettsia salmonis.

    abstract::Piscirickettsia salmonis, an aggressive intracellular pathogen, is the etiological agent of salmonid rickettsial septicemia (SRS). This is a chronic multisystemic disease that generates high mortalities and large losses in Chilean salmon farming, threatening the sustainability of the salmon industry. Previous reports ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.544718

    authors: Pérez-Stuardo D,Espinoza A,Tapia S,Morales-Reyes J,Barrientos C,Vallejos-Vidal E,Sandino AM,Spencer E,Toro-Ascuy D,Rivas-Pardo JA,Reyes-López FE,Reyes-Cerpa S

    更新日期:2020-11-12 00:00:00

  • Cytokine-Regulation of Na+-K+-Cl- Cotransporter 1 and Cystic Fibrosis Transmembrane Conductance Regulator-Potential Role in Pulmonary Inflammation and Edema Formation.

    abstract::Pulmonary edema, a major complication of lung injury and inflammation, is defined as accumulation of extravascular fluid in the lungs leading to impaired diffusion of respiratory gases. Lung fluid balance across the alveolar epithelial barrier protects the distal airspace from excess fluid accumulation and is mainly r...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2017.00393

    authors: Weidenfeld S,Kuebler WM

    更新日期:2017-04-07 00:00:00

  • IL-22: An Underestimated Player in Natural Resistance to Tuberculosis?

    abstract::Approximately 10% of individuals latently infected with Mycobacterium tuberculosis (Mtb) develop active tuberculosis (TB) during their lifetime. Although it is well recognized that T-helper 1 immune responses are crucial for containing latent TB infection, the full array of host factors conferring protective immunity ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.02209

    authors: Ronacher K,Sinha R,Cestari M

    更新日期:2018-09-25 00:00:00

  • Our Evolving Understanding of Kawasaki Disease Pathogenesis: Role of the Gut Microbiota.

    abstract::Kawasaki disease (KD) was first described by Dr. Tomisaku Kawasaki in 1967. The etiology of KD has been studied comprehensively but remains largely unknown. The disease seems to result from the interplay of genetic and environmental susceptibility factors with infectious triggers, followed by a subsequent abnormal imm...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.01616

    authors: Kaneko K,Akagawa S,Akagawa Y,Kimata T,Tsuji S

    更新日期:2020-07-24 00:00:00

  • Previous Radiotherapy Increases the Efficacy of IL-2 in Malignant Pleural Effusion: Potential Evidence of a Radio-Memory Effect?

    abstract::Preclinical and clinical studies have shown that prior receipt of radiotherapy enhances antitumor immune responses, a phenomenon we call the "radio-memory effect." However, all of the evidence regarding this effect to date comes from work with PD1/PDL1 inhibitors. Here we explored whether this effect also occurs with ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,多中心研究

    doi:10.3389/fimmu.2018.02916

    authors: Chen D,Song X,Wang H,Gao Z,Meng W,Chen S,Ma Y,Wang Y,Li K,Yu J,Yue J

    更新日期:2018-12-11 00:00:00