Protection against tuberculosis induced by oral prime with Mycobacterium bovis BCG and intranasal subunit boost based on the vaccine candidate Ag85B-ESAT-6 does not correlate with circulating IFN-γ producing T-cells

Vaccine ◽  
2009 ◽  
Vol 27 (1) ◽  
pp. 28-37 ◽  
Author(s):  
Edgar Badell ◽  
Fabienne Nicolle ◽  
Simon Clark ◽  
Laleh Majlessi ◽  
Frédéric Boudou ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Bovis ◽  
Vaccine Candidate ◽  
Mycobacterium Bovis Bcg ◽  
Ifn Γ

scholarly journals Inhibition of the Multiplication of Mycobacterium leprae by Vaccination with a Recombinant M. bovis BCG Strain That Secretes Major Membrane Protein II in Mice

2009 ◽  
Vol 16 (10) ◽  
pp. 1399-1404 ◽  
Author(s):  
Y. Maeda ◽  
T. Tamura ◽  
M. Matsuoka ◽  
M. Makino
Keyword(s):  
T Cells ◽  
Membrane Protein ◽  
Vector Control ◽  
Mycobacterium Bovis ◽  
Membrane Fraction ◽  
Vaccine Candidate ◽  
Mycobacterium Leprae ◽  
Cytosolic Fraction ◽  
Ifn Γ

ABSTRACT The ability of a recombinant Mycobacterium bovis BCG strain that secretes major membrane protein II (MMP-II) of Mycobacterium leprae (BCG-SM) to confer protection against leprosy was evaluated by use of a mouse footpad model. C57BL/6J mice intradermally inoculated with BCG-SM produced splenic T cells which secreted significant amounts of gamma interferon (IFN-γ) in response to either the recombinant MMP-II, the M. leprae-derived membrane fraction, or the BCG-derived cytosolic fraction in vitro more efficiently than those from the mice infected with the vector control BCG strain (BCG-pMV, a BCG strain containing pMV-261). A higher percentage of CD8+ T cells obtained from BCG-SM-inoculated mice than those obtained from BCG-pMV-inoculated mice produced intracellular IFN-γ on restimulation with the M. leprae antigens. BCG-SM inhibited the multiplication of M. leprae in the footpads of C57BL/6J mice more efficiently than BCG-pMV. These results indicate that a BCG strain that secretes MMP-II could be a better vaccine candidate for leprosy.

scholarly journals Virally Activated CD8 T Cells Home to Mycobacterium bovis BCG-Induced Granulomas but Enhance Antimycobacterial Protection Only in Immunodeficient Mice

2006 ◽  
Vol 75 (3) ◽  
pp. 1154-1166 ◽  
Author(s):  
Laura H. Hogan ◽  
Dominic O. Co ◽  
Jozsef Karman ◽  
Erika Heninger ◽  
M. Suresh ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mycobacterium Bovis ◽  
Cd8 T Cells ◽  
Bacterial Load ◽  
Granulomatous Inflammation ◽  
Cd8 T Cell ◽  
Activated T Cells ◽  
Immunodeficient Mice ◽  
Ifn Γ

ABSTRACT The effect of secondary infections on CD4 T-cell-regulated chronic granulomatous inflammation is not well understood. Here, we have investigated the effect of an acute viral infection on the cellular composition and bacterial protection in Mycobacterium bovis strain bacille Calmette-Guérin (BCG)-induced granulomas using an immunocompetent and a partially immunodeficient murine model. Acute lymphocytic choriomeningitis virus (LCMV) coinfection of C57BL/6 mice led to substantial accumulation of gamma interferon (IFN-γ)-producing LCMV-specific T cells in liver granulomas and increased local IFN-γ. Despite traffic of activated T cells that resulted in a CD8 T-cell-dominated granuloma, the BCG liver organ load was unaltered from control levels. In OT-1 T-cell-receptor (TCR) transgenic mice, ovalbumin (OVA) immunization or LCMV coinfection of BCG-infected mice induced CD8 T-cell-dominated granulomas containing large numbers of non-BCG-specific activated T cells. The higher baseline BCG organ load in this CD8 TCR transgenic animal allowed us to demonstrate that OVA immunization and LCMV coinfection increased anti-BCG protection. The bacterial load remained substantially higher than in mice with a more complete TCR repertoire. Overall, the present study suggests that peripherally activated CD8 T cells can be recruited to chronic inflammatory sites, but their contribution to protective immunity is limited to conditions of underlying immunodeficiency.

scholarly journals Differential Expression of Gamma Interferon mRNA Induced by Attenuated and Virulent Mycobacterium tuberculosis in Guinea Pig Cells after Mycobacterium bovis BCG Vaccination

2003 ◽  
Vol 71 (1) ◽  
pp. 354-364 ◽  
Author(s):  
Amminikutty Jeevan ◽  
Teizo Yoshimura ◽  
Kyeong Eun Lee ◽  
David N. McMurray
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Lymph Node ◽  
Amino Acid ◽  
Guinea Pig ◽  
Mrna Expression ◽  
Mycobacterium Bovis ◽  
Bcg Vaccination ◽  
Lymph Node Cells ◽  
Ifn Γ

ABSTRACT To determine whether Mycobacterium bovis BCG vaccination would alter gamma interferon (IFN-γ) mRNA expression in guinea pig cells exposed to Mycobacterium tuberculosis, we cloned a cDNA encoding guinea pig IFN-γ from a spleen cell cDNA library. The cDNA is composed of 1,110 bp, with an open reading frame encoding a 166-amino-acid protein which shows 56 and 41% amino acid sequence homology to human and mouse IFN-γ, respectively. Spleen or lymph node cells from naïve and BCG-vaccinated guinea pigs were stimulated with purified protein derivative (PPD) or M. tuberculosis H37Ra or H37Rv, and the total RNA was subjected to Northern blot analysis with a 32P-labeled probe derived from the cDNA clone. Compared to the IFN-γ mRNA expression in cells of naïve animals, that in spleen and lymph node cells exposed to various stimuli was enhanced after BCG vaccination. However, there was a significant reduction in IFN-γ mRNA levels when cells were stimulated with a multiplicity of infection of greater than 1 virulent M. tuberculosis bacterium per 10 cells. The enhanced IFN-γ mRNA response in BCG-vaccinated animals was associated with an increase in the proportions of CD4+ T cells in the spleens, as determined by fluorescence-activated cell sorter analysis. Furthermore, the nonadherent population in the spleens enriched either by panning with anti-guinea pig immunoglobulin G-coated plates or by purification on nylon wool columns produced more IFN-γ mRNA than whole spleen cells following stimulation with concanavalin A or PPD. This indicates that T cells are principally responsible for the upregulation of IFN-γ mRNA expression following BCG vaccination. The mechanism by which virulent mycobacteria suppress IFN-γ mRNA accumulation is currently under investigation.

scholarly journals Preexisting Inflammation Due to Mycobacterium bovis BCG Infection Differentially Modulates T-Cell Priming against a Replicating or Nonreplicating Immunogen

2002 ◽  
Vol 70 (4) ◽  
pp. 1957-1964 ◽  
Author(s):  
Renu Dudani ◽  
Yvan Chapdelaine ◽  
Henk van Faassen ◽  
Dean K. Smith ◽  
Hao Shen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mycobacterium Bovis ◽  
Inflammatory Responses ◽  
Protective Efficacy ◽  
T Cell Response ◽  
Boost Vaccine ◽  
Ifn Γ ◽  
T Cell Priming

ABSTRACT Induction of T-cell memory by vaccination ensures long-term protection against pathogens. We determined whether on-going inflammatory responses during vaccination influenced T-cell priming. A preexposure of mice to Mycobacterium bovis BCG impaired their subsequent ability to prime T cells against Listeria monocytogenes. This was characterized by a decrease in L. monocytogenes-specific gamma interferon (IFN-γ)-secreting CD4+ and CD8+ T cells. The intensity of T-cell priming towards L. monocytogenes depended on the extent of L. monocytogenes expansion, and a cessation of this expansion caused by M. bovis BCG-induced inflammation resulted in impairment in T-cell priming. A challenge of M. bovis BCG-infected mice with a higher L. monocytogenes dose increased L. monocytogenes survival and restored T-cell priming towards L. monocytogenes. Impairment in T-cell priming towards L. monocytogenes due to M. bovis BCG-induced inflammation resulted in a compromised protective efficacy in the long term after mice were rechallenged with L. monocytogenes. Preexisting inflammation selectively impaired T-cell priming for replicating immunogens as CD8+ T-cell response to ovalbumin administered as an inert antigen (ovalbumin-archaeosomes) was enhanced by M. bovis BCG preimmunization, whereas priming towards ovalbumin administered as a live immunogen (L. monocytogenes-ovalbumin) was impaired. Thus, depending on the nature of the immunogen, the presence of prior inflammatory responses may either impede or boost vaccine efficacy.

scholarly journals Induction of suppressor T cells in delayed-type hypersensitivity to Mycobacterium bovis BCG in low-responder mice

1980 ◽  
Vol 28 (2) ◽  
pp. 331-335
Author(s):  
R M Nakamura ◽  
T Tokunaga
Keyword(s):  
T Cells ◽  
Mycobacterium Bovis ◽  
Adoptive Transfer ◽  
Suppressor Cells ◽  
Delayed Type Hypersensitivity ◽  
Weak Effect ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Mycobacterium Bovis Bcg ◽  
Low Responder

The induction of delayed-type hypersensitivity to Mycobacterium bovis BCG was specifically inhibited by suppressor T cells in C3H/He, a strain of mice which is a low responder to BCG. The existence of these suppressor cells was confirmed by an adoptive transfer of spleen cells of BCG-injected mice into cyclophosphamide-treated recipients. The suppressor cells appeared in the spleens of the mice 2 to 7 days after intravenous BCG injection. They were sensitive to anti-theta serum and complement and did not adhere to Sephadex G-10. A pretreatment of the mice with cyclophosphamide eliminated the suppression of delayed-type hypersensitivity. These suppressor cells effectively inhibited the induction of delayed-type hypersensitivity to BCG, but showed only weak effect on the expression of it.

scholarly journals Listeria-Vectored Vaccine Expressing the Mycobacterium tuberculosis 30-Kilodalton Major Secretory Protein via the Constitutively Active prfA* Regulon Boosts Mycobacterium bovis BCG Efficacy against Tuberculosis

2017 ◽  
Vol 85 (9) ◽  
Author(s):  
Qingmei Jia ◽  
Barbara Jane Dillon ◽  
Saša Masleša-Galić ◽  
Marcus A. Horwitz
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Mycobacterium Bovis ◽  
Interleukin 2 ◽  
Secretory Protein ◽  
Broth Culture ◽  
Listeriolysin O ◽  
Content Type ◽  
Ifn Γ ◽  
Constitutively Active

ABSTRACT A potent vaccine against tuberculosis, one of the world's deadliest diseases, is needed to enhance the immunity of people worldwide, most of whom have been vaccinated with the partially effective Mycobacterium bovis BCG vaccine. Here we investigate novel live attenuated recombinant Listeria monocytogenes (rLm) vaccines expressing the Mycobacterium tuberculosis 30-kDa major secretory protein (r30/antigen 85B [Ag85B]) (rLm30) as heterologous booster vaccines in animals primed with BCG. Using three attenuated L. monocytogenes vectors, L. monocytogenes ΔactA (LmI), L. monocytogenes ΔactA ΔinlB (LmII), and L. monocytogenes ΔactA ΔinlB prfA* (LmIII), we constructed five rLm30 vaccine candidates expressing r30 linked in frame to the L. monocytogenes listeriolysin O signal sequence and driven by the hly promoter (h30) or linked in frame to the ActA N-terminal 100 amino acids and driven by the actA promoter (a30). All five rLm30 vaccines secreted r30 in broth and macrophages; while rLm30 expressing r30 via a constitutively active prfA* regulon (rLmIII/a30) expressed the largest amount of r30 in broth culture, all five rLm30 vaccines expressed equivalent amounts of r30 in infected macrophages. In comparative studies, boosting of BCG-immunized mice with rLmIII/a30 induced the strongest antigen-specific T-cell responses, including splenic and lung polyfunctional CD4+ T cells expressing the three cytokines interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin-2 (IL-2) (P < 0.001) and splenic and lung CD8+ T cells expressing IFN-γ (P < 0.0001). In mice and guinea pigs, the rLmIII/a30 and rLmI/h30 vaccines were generally more potent booster vaccines than r30 with an adjuvant and a recombinant adenovirus vaccine expressing r30. In a setting in which BCG alone was highly immunoprotective, boosting of mice with rLmIII/a30, the most potent of the vaccines, significantly enhanced protection against aerosolized M. tuberculosis (P < 0.01).

scholarly journals Antigen-Specific IFN-γ/IL-17-Co-Producing CD4+ T-Cells are the Determinants for Protective Efficacy of Tuberculosis Subunit Vaccine

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 300 ◽  
Author(s):  
Han-Gyu Choi ◽  
Kee Woong Kwon ◽  
Seunga Choi ◽  
Yong Woo Back ◽  
Hye-Soo Park ◽  
...  
Keyword(s):  
T Cells ◽  
Subunit Vaccine ◽  
Vaccine Candidate ◽  
Protective Efficacy ◽  
Lung Cells ◽  
Bacillus Calmette Guerin ◽  
Post Challenge ◽  
Subunit Vaccines ◽  
Ifn Γ

The antigen-specific Th17 responses in the lungs for improved immunity against Mycobacterium tuberculosis (Mtb) infection are incompletely understood. Tuberculosis (TB) vaccine candidate HSP90-ESAT-6 (E6), given as a Bacillus Calmette-Guérin (BCG)-prime boost regimen, confers superior long-term protection against the hypervirulent Mtb HN878 infection, compared to BCG or BCG-E6. Taking advantage of protective efficacy lead-out, we found that ESAT-6-specific multifunctional CD4+IFN-γ+IL-17+ T-cells optimally correlated with protection level against Mtb infection both pre-and post-challenge. Macrophages treated with the supernatant of re-stimulated lung cells from HSP90-E6-immunised mice significantly restricted Mtb growth, and this phenomenon was abrogated by neutralising anti-IFN-γ and/or anti-IL-17 antibodies. We identified a previously unrecognised role for IFN-γ/IL-17 synergism in linking anti-mycobacterial phagosomal activity to enhance host control against Mtb infection. The implications of our findings highlight the fundamental rationale for why and how Th17 responses are essential in the control of Mtb, and for the development of novel anti-TB subunit vaccines.

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