scholarly journals Humoral and Cellular Immune Responses in Mice Immunized with Recombinant Mycobacterium bovis Bacillus Calmette-Guérin Producing a Pertussis Toxin-Tetanus Toxin Hybrid Protein

1999 ◽  
Vol 67 (10) ◽  
pp. 5100-5105 ◽  
Author(s):  
B. Abomoelak ◽  
K. Huygen ◽  
L. Kremer ◽  
M. Turneer ◽  
C. Locht
Keyword(s):  
Immune Response ◽  
Mycobacterium Bovis ◽  
Pertussis Toxin ◽  
Tetanus Toxin ◽  
Expression System ◽  
Interleukin 2 ◽  
Hybrid Protein ◽  
Acellular Vaccines ◽  
Cellular Immune

ABSTRACT The development of combined vaccines constitutes one of the priorities in modern vaccine research. One of the most successful combined vaccines in use is the diphtheria-pertussis-tetanus vaccine. However, concerns about the safety of the pertussis arm have led to decreased acceptance of the vaccine but also to the development of new, safer, and effective acellular vaccines against pertussis. Unfortunately, the production cost of these new vaccines is significantly higher than that of previous vaccines. Here, we explore the potential of live recombinant Mycobacterium bovis BCG producing the hybrid protein S1-TTC, which contains the S1 subunit of pertussis toxin fused to fragment C of tetanus toxin, as an alternative to the acellular vaccines. S1-TTC was produced in two different expression systems. In the first system its production was under the control of the 85A antigen promoter and signal peptide, and in the second system it was under the control of the hsp60promoter. Although expression of the hybrid antigen was obtained in both cases, only the second expression system yielded a recombinant BCG strain able to induce both a specific humoral immune response and a specific cellular immune response. The antibodies generated were directed against the TTC part and neutralized toxin activity in an in vivo challenge model, whereas interleukin-2 production was specific for both parts of the molecule. Since protection against tetanus is antibody mediated and protection against pertussis may be cell mediated, this constitutes a first promising step towards the development of a cost-effective, protective, and safe combined vaccine against pertussis, tetanus, and tuberculosis.

scholarly journals Kallikrein 12 Regulates Innate Resistance of Murine Macrophages against Mycobacterium bovis Infection by Modulating Autophagy and Apoptosis

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 415 ◽  
Author(s):  
Naveed Sabir ◽  
Tariq Hussain ◽  
Yi Liao ◽  
Jie Wang ◽  
Yinjuan Song ◽  
...  
Keyword(s):  
Immune Response ◽  
Mycobacterium Bovis ◽  
Serine Proteases ◽  
New Paradigm ◽  
Murine Macrophages ◽  
Immune Response Regulation ◽  
The Difference

Mycobacterium bovis (M. bovis) is a member of the Mycobacterium tuberculosis (Mtb) complex causing bovine tuberculosis (TB) and imposing a high zoonotic threat to human health. Kallikreins (KLKs) belong to a subgroup of secreted serine proteases. As their role is established in various physiological and pathological processes, it is likely that KLKs expression may mediate a host immune response against the M. bovis infection. In the current study, we report in vivo and in vitro upregulation of KLK12 in the M. bovis infection. To define the role of KLK12 in immune response regulation of murine macrophages, we produced KLK12 knockdown bone marrow derived macrophages (BMDMs) by using siRNA transfection. Interestingly, the knockdown of KLK12 resulted in a significant downregulation of autophagy and apoptosis in M. bovis infected BMDMs. Furthermore, we demonstrated that this KLK12 mediated regulation of autophagy and apoptosis involves mTOR/AMPK/TSC2 and BAX/Bcl-2/Cytochrome c/Caspase 3 pathways, respectively. Similarly, inflammatory cytokines IL-1β, IL-6, IL-12 and TNF-α were significantly downregulated in KLK12 knockdown macrophages but the difference in IL-10 and IFN-β expression was non-significant. Taken together, these findings suggest that upregulation of KLK12 in M. bovis infected murine macrophages plays a substantial role in the protective immune response regulation by modulating autophagy, apoptosis and pro-inflammatory pathways. To our knowledge, this is the first report on expression and the role of KLK12 in the M. bovis infection and the data may contribute to a new paradigm for diagnosis and treatment of bovine TB.

scholarly journals A targeted complement-dependent strategy to improve the outcome of mAb therapy, and characterization in a murine model of metastatic cancer

Blood ◽  
2012 ◽  
Vol 119 (25) ◽  
pp. 6043-6051 ◽  
Author(s):  
Michelle Elvington ◽  
Yuxiang Huang ◽  
B. Paul Morgan ◽  
Fei Qiao ◽  
Nico van Rooijen ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Cell ◽  
Complement Activation ◽  
Metastatic Cancer ◽  
Protein Targets ◽  
Complement Inhibitors ◽  
Activation Products ◽  
Cellular Immune

Abstract Complement inhibitors expressed on tumor cells provide an evasion mechanism against mAb therapy and may modulate the development of an acquired antitumor immune response. Here we investigate a strategy to amplify mAb-targeted complement activation on a tumor cell, independent of a requirement to target and block complement inhibitor expression or function, which is difficult to achieve in vivo. We constructed a murine fusion protein, CR2Fc, and demonstrated that the protein targets to C3 activation products deposited on a tumor cell by a specific mAb, and amplifies mAb-dependent complement activation and tumor cell lysis in vitro. In syngeneic models of metastatic lymphoma (EL4) and melanoma (B16), CR2Fc significantly enhanced the outcome of mAb therapy. Subsequent studies using the EL4 model with various genetically modified mice and macrophage-depleted mice revealed that CR2Fc enhanced the therapeutic effect of mAb therapy via both macrophage-dependent FcγR-mediated antibody-dependent cellular cytotoxicity, and by direct complement-mediated lysis. Complement activation products can also modulate adaptive immunity, but we found no evidence that either mAb or CR2Fc treatment had any effect on an antitumor humoral or cellular immune response. CR2Fc represents a potential adjuvant treatment to increase the effectiveness of mAb therapy of cancer.

scholarly journals IFN-α Boosting of Mycobacterium bovis Bacillus Calmette Güerin-Vaccine Promoted Th1 Type Cellular Response and Protection against M. tuberculosis Infection

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
C. E. Rivas-Santiago ◽  
G. G. Guerrero
Keyword(s):  
Immune Response ◽  
Mycobacterium Bovis ◽  
Cellular Immune Response ◽  
Cellular Response ◽  
Bacterial Load ◽  
Bcg Vaccine ◽  
Type I ◽  
Bacillus Calmette Guerin ◽  
Type I Ifns ◽  
Cellular Immune

The role of type I IFNs in the pathogenesis and control of mycobacterial infection is still controversial. It has been reported that type I IFNs exacerbated M. tuberculosis infection through hampering Th1 type cellular immune response. However, under certain conditions they can act as natural immune adjuvants for commercial vaccines. At this point, we have reported recently that successive IFN-alpha boosting of Mycobacterium bovis Bacillus Calmette Güerin (BCG) vaccinated mice protected adult mice from intradermal M. lepraemurium infection and a difference in iNOS was observed. In the present work, we have found that intramuscular IFN-α boosting of Mycobacterium bovis Bacillus Calmette Güerin (BCG) vaccine, either in vitro (human cell line or macrophages derived from PBMC) or in vivo (aerosol mouse model of MTb infection), promoted mostly the development of specific anti-antimycobacterial Th1 type cytokines (IFN-γ; IL-12, TNF-alpha, and IL-17; IL1β) while bacterial load reduction (0.9 logs versus PBS or BCG vaccine) was observed. These findings indicate that, under the experimental settings reported here, interferon alpha can drive or affect the TH cellular immune response in favour of BCG-inducing immunity against M. tuberculosis infection.

scholarly journals Cellular Immune Response Against Firefly Luciferase After Sleeping Beauty–Mediated Gene Transfer In Vivo

2014 ◽  
Vol 25 (11) ◽  
pp. 955-965 ◽  
Author(s):  
Kelly M. Podetz-Pedersen ◽  
Vaiva Vezys ◽  
Nikunj V. Somia ◽  
Stephen J. Russell ◽  
R. Scott McIvor
Keyword(s):  
Immune Response ◽  
Gene Transfer ◽  
Cellular Immune Response ◽  
Firefly Luciferase ◽  
Sleeping Beauty ◽  
Cellular Immune
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