Antigen 85 complex as a powerful Mycobacterium tuberculosis immunogene: Biology, immune-pathogenicity, applications in diagnosis, and vaccine design

2017 ◽  
Vol 112 ◽  
pp. 20-29 ◽  
Author(s):  
Mohsen Karbalaei Zadeh Babaki ◽  
Saman Soleimanpour ◽  
Seyed Abdolrahim Rezaee
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Vaccine Design ◽  
Antigen 85

scholarly journals Lessons from Bacillus Calmette-Guérin: Harnessing Trained Immunity for Vaccine Development

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2109
Author(s):  
Samuel T. Pasco ◽  
Juan Anguita
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Vaccine Development ◽  
Vaccine Design ◽  
Innate Immune ◽  
Bacillus Calmette Guerin ◽  
Adaptive Immune Responses ◽  
Trained Immunity ◽  
Adaptive Immune ◽  
Potential Methods

Vaccine design traditionally focuses on inducing adaptive immune responses against a sole target pathogen. Considering that many microbes evade innate immune mechanisms to initiate infection, and in light of the discovery of epigenetically mediated innate immune training, the paradigm of vaccine design has the potential to change. The Bacillus Calmette-Guérin (BCG) vaccine induces some level of protection against Mycobacterium tuberculosis (Mtb) while stimulating trained immunity that correlates with lower mortality and increased protection against unrelated pathogens. This review will explore BCG-induced trained immunity, including the required pathways to establish this phenotype. Additionally, potential methods to improve or expand BCG trained immunity effects through alternative vaccine delivery and formulation methods will be discussed. Finally, advances in new anti-Mtb vaccines, other antimicrobial uses for BCG, and “innate memory-based vaccines” will be examined.

scholarly journals Isoniazid induces expression of the antigen 85 complex in Mycobacterium tuberculosis.

1996 ◽  
Vol 40 (7) ◽  
pp. 1754-1756 ◽  
Author(s):  
T R Garbe ◽  
N S Hibler ◽  
V Deretic
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Antimicrobial Agents ◽  
Isonicotinic Acid ◽  
Acid Hydrazide ◽  
Isonicotinic Acid Hydrazide ◽  
Two Dimensional Gel Electrophoresis ◽  
Mycolic Acids ◽  
Mycobacterium Tuberculosis H37rv ◽  
Antigen 85 ◽  
Differential Gene

Exposure to isoniazid induced the expression of several secreted proteins in Mycobacterium tuberculosis H37Rv. Two-dimensional gel electrophoresis and immunoblot analyses indicated that two of the prominent isonicotinic acid hydrazide-inducible polypeptides were members of the antigen 85 complex, recently demonstrated to have mycolyltransferase activity. We postulate the existence of an intermediate, whose production is inhibited by isonicotinic acid hydrazide, which plays a negative feedback regulatory role in the metabolism of mycolic acids are revealed by the overexpression of the antigen 85 complex. The approach described here relies on analyses of differential gene expression following exposure to inhibitors and may become a more general tool in dissecting the effects of antimicrobial agents.

Florid pulmonary inflammatory responses in mice vaccinated with Antigen-85 pulsed dendritic cells and challenged by aerosol with Mycobacterium tuberculosis

2002 ◽  
Vol 220 (1) ◽  
pp. 13-19 ◽  
Author(s):  
Mercedes González-Juarrero ◽  
Joanne Turner ◽  
Randall J. Basaraba ◽  
John T. Belisle ◽  
Ian M. Orme
Keyword(s):  
Dendritic Cells ◽  
Mycobacterium Tuberculosis ◽  
Inflammatory Responses ◽  
Antigen 85

scholarly journals Induction of Protective Cellular Immunity against Mycobacterium tuberculosis by Recombinant Attenuated Self-Destructing Listeria monocytogenes Strains Harboring Eukaryotic Expression Plasmids for Antigen 85 Complex and MPB/MPT51

2004 ◽  
Vol 72 (4) ◽  
pp. 2014-2021 ◽  
Author(s):  
Keita Miki ◽  
Toshi Nagata ◽  
Takao Tanaka ◽  
Yeung-Hyen Kim ◽  
Masato Uchijima ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Listeria Monocytogenes ◽  
Cellular Immunity ◽  
Protective Antigen ◽  
Mycobacterial Infection ◽  
Eukaryotic Expression ◽  
Recombinant Bacteria ◽  
Antigen 85 ◽  
Expression Plasmids ◽  
Mycobacterial Protein

ABSTRACT We report here the induction of specific protective cellular immunity against Mycobacterium tuberculosis by the employment of vaccination with recombinant attenuated Listeria monocytogenes strains. We constructed self-destructing attenuated L. monocytogenes Δ2 strains carrying eukaryotic expression plasmids for the antigen 85 complex (Ag85A and Ag85B) and for MPB/MPT51 (mycobacterial protein secreted by M. bovis BCG/mycobacterial protein secreted by M. tuberculosis) molecules. Infection of these recombinant bacteria allowed expression of the genes in the J774A.1 murine macrophage cell line. Intraperitoneal vaccination of C57BL/6 mice with these recombinant bacteria was capable of inducing purified protein derivative-specific cellular immune responses, such as foot pad reactions, proliferative responses of splenocytes, and gamma interferon production from splenocytes, suggesting the efficacy of vaccination against mycobacterial infection by use of these recombinant L. monocytogenes strains. Furthermore, intravenous vaccination with recombinant bacteria carrying expression plasmids for Ag85A, Ag85B, or MPB/MPT51 in BALB/c mice elicited significant protective responses, comparable to those evoked by a live Mycobacterium bovis BCG vaccine. Notably, this is the first report to show that MPB/MPT51 is a major protective antigen in addition to Ag85A and Ag85B, which have been reported to be major mycobacterial protective antigens.

scholarly journals Identification and Characterization of a 29-Kilodalton Protein from Mycobacterium tuberculosis Culture Filtrate Recognized by Mouse Memory Effector Cells

1998 ◽  
Vol 66 (6) ◽  
pp. 2728-2735 ◽  
Author(s):  
Ida Rosenkrands ◽  
Peter Birk Rasmussen ◽  
Markus Carnio ◽  
Susanne Jacobsen ◽  
Michael Theisen ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Animal Models ◽  
Molecular Mass ◽  
Culture Filtrate ◽  
Protective Immunity ◽  
Short Term ◽  
Effector Cells ◽  
Antigen 85 ◽  
Short Term Culture

ABSTRACT Culture filtrate proteins from Mycobacterium tuberculosis induce protective immunity in various animal models of tuberculosis. Two molecular mass regions (6 to 10 kDa and 24 to 36 kDa) of short-term culture filtrate are preferentially recognized by Th1 cells in animal models as well as by patients with minimal disease. In the present study, the 24- to 36-kDa region has been studied, and the T-cell reactivity has been mapped in detail. Monoclonal antibodies were generated, and one monoclonal antibody, HYB 71-2, with reactivity against a 29-kDa antigen located in the highly reactive region below the antigen 85 complex was selected. The 29-kDa antigen (CFP29) was purified from M. tuberculosis short-term culture filtrate by thiophilic adsorption chromatography, anion-exchange chromatography, and gel filtration. In its native form, CFP29 forms a polymer with a high molecular mass. CFP29 was mapped in two-dimensional electrophoresis gels as three distinct spots just below the antigen 85 complex component MPT59. CFP29 is present in both culture filtrate and the membrane fraction from M. tuberculosis, suggesting that this antigen is released from the envelope to culture filtrate during growth. Determination of the N-terminal amino acid sequence allowed cloning and sequencing of the cfp29 gene. The nucleotide sequence showed 62% identity to the bacteriocin Linocin fromBrevibacterium linens. Purified recombinant histidine-tagged CFP29 and native CFP29 had similar T-cell stimulatory properties, and they both elicited the release of high levels of gamma interferon from mouse memory effector cells isolated during the recall of protective immunity to tuberculosis. Interspecies analysis by immunoblotting and PCR demonstrated that CFP29 is widely distributed in mycobacterial species.

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