scholarly journals Vaccination of Guinea Pigs with DNA Encoding the Mycobacterial Antigen MPB83 Influences Pulmonary Pathology but Not Hematogenous Spread following Aerogenic Infection with Mycobacterium bovis

2002 ◽  
Vol 70 (4) ◽  
pp. 2159-2165 ◽  
Author(s):  
Mark A. Chambers ◽  
Ann Williams ◽  
Graham Hatch ◽  
Dolores Gavier-Widén ◽  
Graham Hall ◽  
...  
Keyword(s):  
Mycobacterium Bovis ◽  
Guinea Pigs ◽  
Vaccination Strategy ◽  
Control Program ◽  
Dna Vaccination ◽  
Mycobacterial Antigen ◽  
Lung Pathology ◽  
Dna Encoding ◽  
Hematogenous Spread ◽  
Bcg Vaccination

ABSTRACT Protection of cattle against bovine tuberculosis by vaccination could be an important control strategy in countries where there is persistent Mycobacterium bovis infection in wildlife and in developing countries where it is not economical to implement a tuberculin test and slaughter control program. The main aim of such a vaccination strategy would be to reduce transmission of infection by reducing the lung pathology caused by infection and preventing seeding of the organism to organs from which M. bovis could be excreted. Recent reports of successful DNA vaccination against Mycobacterium tuberculosis in small-animal models have suggested that DNA vaccines act by reducing lung pathology without sensitizing animals to tuberculin testing. We therefore evaluated the ability of vaccines consisting of DNA encoding the mycobacterial antigens MPB83 and 85A to reduce lung pathology and prevent hematogenous spread in guinea pigs challenged with a low dose of aerosolized M. bovis. Vaccination with MPB83 DNA reduced the severity of pulmonary lesions, as assessed by histopathology, and resembled M. bovis BCG vaccination in this respect. However, unlike BCG vaccination, MPB83 DNA vaccination did not protect challenged guinea pigs from hematogenous spread of organisms to the spleen. In contrast, vaccination with antigen 85A DNA, a promising DNA vaccine for human tuberculosis, had no measurable protective effect against infection with M. bovis.

scholarly journals Influence of Mycobacterium bovis BCG Vaccination on Cellular Immune Response of Guinea Pigs Challenged with Mycobacterium tuberculosis

2008 ◽  
Vol 15 (8) ◽  
pp. 1248-1258 ◽  
Author(s):  
Diane Ordway ◽  
Marcela Henao-Tamayo ◽  
Crystal Shanley ◽  
Erin E. Smith ◽  
Gopinath Palanisamy ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Mycobacterium Bovis ◽  
Guinea Pigs ◽  
Lung Damage ◽  
Cell Populations ◽  
Lung Pathology ◽  
Bcg Vaccination ◽  
Macrophage Populations ◽  
Cellular Immune

ABSTRACT Mycobacterium bovis bacillus Calmette-Guérin (BCG) currently remains the only licensed vaccine for the prevention of tuberculosis. In this study, we used a newly described flow cytometric technique to monitor changes in cell populations accumulating in the lungs and lymph nodes of naïve and vaccinated guinea pigs challenged by low-dose aerosol infection with virulent Mycobacterium tuberculosis. As anticipated, vaccinated guinea pigs controlled the growth of the challenge infection more efficiently than controls did. This early phase of bacterial control in immune animals was associated with increased accumulation of CD4 and CD8 T cells, including cells expressing the activation marker CD45, as well as macrophages expressing class II major histocompatibility complex molecules. As the infection continued, the numbers of T cells in the lungs of vaccinated animals waned, whereas the numbers of these cells expressing CD45 increased. Whereas BCG vaccination reduced the influx of heterophils (neutrophils) into the lungs, an early B-cell influx was observed in these vaccinated animals. Overall, vaccine protection was associated with reduced pathology and lung damage in the vaccinated animals. These data provide the first direct evidence that BCG vaccination accelerates the influx of protective T-cell and macrophage populations into the infected lungs, diminishes the accumulation of nonprotective cell populations, and reduces the severity of lung pathology.

scholarly journals Environmental Strains of Mycobacterium avium Interfere with Immune Responses Associated with Mycobacterium bovis BCG Vaccination

2007 ◽  
Vol 75 (6) ◽  
pp. 2833-2840 ◽  
Author(s):  
Sarah L. Young ◽  
Lynn Slobbe ◽  
Rachel Wilson ◽  
Bryce M. Buddle ◽  
Geofferey W. de Lisle ◽  
...  
Keyword(s):  
Immune System ◽  
Mycobacterium Bovis ◽  
Mycobacterium Avium ◽  
Growth Characteristics ◽  
Mycobacterial Antigen ◽  
Serological Response ◽  
Necrosis Factor Alpha ◽  
Activation Markers ◽  
Bcg Vaccination

ABSTRACT Prior exposure of a vaccinee to certain species of environmental mycobacteria can prime the immune system against common mycobacterial antigens, which can in turn reduce the subsequent efficacy of live attenuated mycobacterial vaccines (such as Mycobacterium bovis BCG), in both human and livestock vaccination programs. In this study, two strains of Mycobacterium avium, both isolated from New Zealand livestock, were investigated to determine their growth characteristics and effects on the immune system in murine models. Markedly different effects on the immune system were observed; an IS901-negative strain (WAg 207) induced significant up-regulation of cell surface activation markers (major histocompatibility complex II, CD80, and CD86) on in vitro-derived dendritic cells and induced the release of proinflammatory monokines (interleukin-1β [IL-1β], IL-6, and tumor necrosis factor alpha) in dendritic cell-macrophage cocultures following direct in vitro contact of cells with bacteria. In contrast, an IS901-positive strain (WAg 206) had none of these effects. When mice were exposed to M. avium via oral infection prior to BCG parenteral immunization, both strains were shown to be capable of decreasing subsequent antigen-stimulated gamma interferon secretion by splenic lymphocytes, although this effect was more significant for strain WAg 206. Both strains also induced a mycobacterial antigen-specific serological response in M. avium-sensitized and BCG-immunized mice; this response was greater in WAg 206-sensitized mice, and there was a predominance of immunoglobulin G1 antibody. The down-regulation of IFN-γ responses and the up-regulation of antibody responses are characteristic of a switch to a type 2 immune response. The different results may be linked to the inherent growth characteristics of the two strains, since WAg 206 was shown to grow slowly in murine macrophages in vitro and to cause a persistent systemic infection following infection in vivo, while WAg 207 grew fast and did not persist in mice. The implications of these findings for BCG vaccination protocols are discussed.

Mycobacterium bovis BCG vaccination modulates TNF-α production after pulmonary challenge with virulent Mycobacterium tuberculosis in guinea pigs

Tuberculosis ◽  
2007 ◽  
Vol 87 (2) ◽  
pp. 155-165 ◽  
Author(s):  
Toshiko Yamamoto ◽  
Todd M. Lasco ◽  
Kazuyuki Uchida ◽  
Yoshitaka Goto ◽  
Amminikutty Jeevan ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Bovis ◽  
Guinea Pigs ◽  
Mycobacterium Bovis Bcg ◽  
Bcg Vaccination ◽  
Tnf Α

scholarly journals Cloning of the Gene Encoding a 22-Kilodalton Cell Surface Antigen of Mycobacterium bovisBCG and Analysis of Its Potential for DNA Vaccination against Tuberculosis

2000 ◽  
Vol 68 (3) ◽  
pp. 1040-1047 ◽  
Author(s):  
Philippe Lefèvre ◽  
Olivier Denis ◽  
Lucas De Wit ◽  
Audrey Tanghe ◽  
Paul Vandenbussche ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Genomic Library ◽  
Signal Sequence ◽  
Interleukin 2 ◽  
Dna Vaccination ◽  
Mouse Strains ◽  
Mycobacterial Antigen ◽  
Cell Fractionation ◽  
Dna Encoding ◽  
Gene Encoding

ABSTRACT Using spleen cells from mice vaccinated with liveMycobacterium bovis BCG, we previously generated three monoclonal antibodies reactive against a 22-kDa protein present in mycobacterial culture filtrate (CF) (K. Huygen et al., Infect. Immun. 61:2687–2693, 1993). These monoclonal antibodies were used to screen an M. bovis BCG genomic library made in phage λgt11. The gene encoding a 233-amino-acid (aa) protein, including a putative 26-aa signal sequence, was isolated, and sequence analysis indicated that the protein was 98% identical with the M. tuberculosis Lppx protein and that it contained a sequence 94% identical with the M. leprae 38-mer polypeptide 13B3 recognized by T cells from killed M. leprae-immunized subjects. Flow cytometry and cell fractionation demonstrated that the 22-kDa CF protein is also highly expressed in the bacterial cell wall and membrane compartment but not in the cytosol. C57BL/6, C3H, and BALB/c mice were vaccinated with plasmid DNA encoding the 22-kDa protein and analyzed for immune response and protection against intravenous M. tuberculosis challenge. Whereas DNA vaccination induced elevated antibody responses in C57BL/6 and particularly in C3H mice, Th1-type cytokine response, as measured by interleukin-2 and gamma interferon secretion, was only modest, and no protection against intravenous M. tuberculosis challenge was observed in any of the three mouse strains tested. Therefore, the 22-kDa antigen seems to have little potential for a DNA vaccine against tuberculosis, but it may be a good candidate for a mycobacterial antigen detection test.

scholarly journals Immune Responses Induced in Cattle by Vaccination with a Recombinant Adenovirus Expressing Mycobacterial Antigen 85A and Mycobacterium bovis BCG

2006 ◽  
Vol 74 (2) ◽  
pp. 1416-1418 ◽  
Author(s):  
H. Martin Vordermeier ◽  
Kris Huygen ◽  
Mahavir Singh ◽  
R. Glyn Hewinson ◽  
Zhou Xing
Keyword(s):  
Immune Responses ◽  
Mycobacterium Bovis ◽  
Recombinant Adenovirus ◽  
Gamma Interferon ◽  
Mycobacterial Antigen ◽  
Mycobacterium Bovis Bcg ◽  
Bcg Vaccination ◽  
Interferon Responses

ABSTRACT Cattle were vaccinated with an adenovirus expressing the mycobacterial antigen 85A (rAd85A), with Mycobacterium bovis BCG followed by rAd85A heterologous boosting, or with rAd85A followed by BCG boosting. BCG/rAd85A resulted in the highest direct gamma interferon responses. Cultured enzyme-linked immunospot assay analysis demonstrated that memory responses were induced by all three protocols but were strongest after BCG/rAd85A and rAd85A/BCG vaccination.

scholarly journals The Protective Effect of the Mycobacterium bovis BCG Vaccine Is Increased by Coadministration with the Mycobacterium tuberculosis 72-Kilodalton Fusion Polyprotein Mtb72F in M. tuberculosis-Infected Guinea Pigs

2004 ◽  
Vol 72 (11) ◽  
pp. 6622-6632 ◽  
Author(s):  
Lise Brandt ◽  
Yasir A. W. Skeiky ◽  
Mark R. Alderson ◽  
Yves Lobet ◽  
Wilfried Dalemans ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Guinea Pig ◽  
Mycobacterium Bovis ◽  
Guinea Pigs ◽  
Airway Remodeling ◽  
Bacterial Load ◽  
Bcg Vaccine ◽  
Protective Capacity ◽  
Bcg Vaccination ◽  
Lung Consolidation

ABSTRACT A tuberculosis vaccine candidate consisting of a 72-kDa polyprotein or fusion protein based upon the Mtb32 and Mtb39 antigens of Mycobacterium tuberculosis and designated Mtb72F was tested for its protective capacity as a potential adjunct to the Mycobacterium bovis BCG vaccine in the mouse and guinea pig models of this disease. Formulation of recombinant Mtb72F (rMtb72F) in an AS02A adjuvant enhanced the Th1 response to BCG in mice but did not further reduce the bacterial load in the lungs after aerosol challenge infection. In the more stringent guinea pig disease model, rMtb72F delivered by coadministration with BCG vaccination significantly improved the survival of these animals compared to BCG alone, with some animals still alive and healthy in their appearance at >100 weeks post-aerosol challenge. A similar trend was observed with guinea pigs in which BCG vaccination was boosted by DNA vaccination, although this increase was not statistically significant due to excellent protection conferred by BCG alone. Histological examination of the lungs of test animals indicated that while BCG controls eventually died from overwhelming lung consolidation, the majority of guinea pigs receiving BCG mixed with rMtb72F or boosted twice with Mtb72F DNA had mostly clear lungs with minimal granulomatous lesions. Lesions were still prominent in guinea pigs receiving BCG and the Mtb72F DNA boost, but there was considerable evidence of lesion healing and airway remodeling and reestablishment. These data support the hypothesis that the coadministration or boosting of BCG vaccination with Mtb72F may limit the lung consolidation seen with BCG alone and may promote lesion resolution and healing. Collectively, these data suggest that enhancing BCG is a valid vaccination strategy for tuberculosis that is worthy of clinical evaluation.

scholarly journals Kinetics of the Immune Response Profile in Guinea Pigs after Vaccination with Mycobacterium bovis BCG and Infection with Mycobacterium tuberculosis

2009 ◽  
Vol 77 (11) ◽  
pp. 4837-4846 ◽  
Author(s):  
Ajay Grover ◽  
Jennifer Taylor ◽  
JoLynn Troudt ◽  
Andrew Keyser ◽  
Kimberly Arnett ◽  
...  
Keyword(s):  
T Cells ◽  
Mrna Expression ◽  
Mycobacterium Bovis ◽  
T Cell Activation ◽  
Guinea Pigs ◽  
Cell Activation ◽  
Activated T Cells ◽  
Bcg Vaccination ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT The guinea pig model of tuberculosis is used extensively in assessing novel vaccines, since Mycobacterium bovis BCG vaccination effectively prolongs survival after low-dose aerosol infection with virulent M. tuberculosis. To better understand how BCG extends time to death after pulmonary infection with M. tuberculosis, we examined cytokine responses postvaccination and recruitment of activated T cells and cytokine response postinfection. At 10 weeks postvaccination, splenic gamma interferon (IFN-γ) mRNA was significantly elevated compared to the levels at 5 weeks in ex vivo stimulation assays. At 15, 40, 60, and 120 days postinfection, T-cell activation (CD4+ CD62Llow and CD8+ CD62Llow) and mRNA expression of IFN-γ, tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), IL-10, IL-12, and eomesodermin were assessed. Our data show that at day 40, BCG-vaccinated guinea pigs had significantly increased levels of IFN-γ mRNA expression but decreased TNF-α mRNA expression in their lungs compared to the levels in nonvaccinated animals. At day 120, a time when nonvaccinated guinea pigs succumbed to infection, low levels of IFN-γ mRNA were observed even though there were increasing levels of IL-1, IL-12, and IL-10, and the numbers of activated T cells did not differ from those in BCG-vaccinated animals. BCG vaccination conferred the advantage of recruiting greater numbers of CD4+ CD62Llow T cells at day 40, although the numbers of CD8+ CD62Llow T cells were not elevated compared to the numbers in nonvaccinated animals. Our data suggest that day 40 postinfection may be a pivotal time point in determining vaccine efficacy and prolonged survival and that BCG promotes the capacity of T cells in the lungs to respond to infection.

scholarly journals Lack of Immune Responses to Mycobacterium tuberculosis DosR Regulon Proteins following Mycobacterium bovis BCG Vaccination

2007 ◽  
Vol 75 (7) ◽  
pp. 3523-3530 ◽  
Author(s):  
May Young Lin ◽  
Annemieke Geluk ◽  
Steven G. Smith ◽  
Amanda L. Stewart ◽  
Annemieke H. Friggen ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Mycobacterium Bovis ◽  
Protective Efficacy ◽  
Transcriptional Profiling ◽  
In Silico Analysis ◽  
Dna Encoding ◽  
Bcg Vaccination ◽  
Dosr Regulon

ABSTRACT Mycobacterium bovis BCG is widely used as a vaccine against tuberculosis (TB), despite its variable protective efficacy. Relatively little is known about the immune response profiles following BCG vaccination in relation to protection against TB. Here we tested whether BCG vaccination results in immune responses to DosR (Rv3133c) regulon-encoded proteins. These so-called TB latency antigens are targeted by the immune system during persistent Mycobacterium tuberculosis infection and have been associated with immunity against latent M. tuberculosis infection. In silico analysis of the DosR regulon in BCG and M. tuberculosis showed at least 97% amino acid sequence homology, with 41 out of 48 genes being identical. Transcriptional profiling of 14 different BCG strains, under hypoxia and nitric oxide exposure in vitro, revealed a functional DosR regulon similar to that observed in M. tuberculosis. Next, we assessed human immune responses to a series of immunodominant TB latency antigens and found that BCG vaccination fails to induce significant responses to latency antigens. Similar results were obtained with BCG-vaccinated BALB/c mice. In contrast, responses to latency antigens were observed in individuals with suspected exposure to TB (as indicated by positive gamma interferon responses to TB-specific antigens ESAT-6 and CFP-10) and in mice vaccinated with plasmid DNA encoding selected latency antigens. Since immune responses to TB latency antigens have been associated with control of latent M. tuberculosis infection, our findings support the development of vaccination strategies incorporating DosR regulon antigens to complement and improve the current BCG vaccine.

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