Preventing Tuberculosis with Bacillus Calmette-Guérin Vaccine: A Meta-Analysis of the Literature

Brewer, Timothy F.

doi:10.1086/314072

Cited by 241 publications

(160 citation statements)

References 22 publications

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“…We have selected for this purpose the inoculation of mice with Bacillus Calmette-Guerin (BCG), an attenuated form of Mycobacterium bovis that is used in several countries outside the United States as a vaccine for tuberculosis (Brewer, 2000). Intraperitoneal administration of BCG to mice is rapidly followed by long-lasting mycobacterial dissemination in all organs (particularly the lungs) except the brain (Tsenova et al, 1999) and by a drastic increase in circulating IFN-γ (Sander et al, 1995), a key cytokine for the activation of IDO (Takikawa et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Inoculation of Bacillus Calmette-Guerin to mice induces an acute episode of sickness behavior followed by chronic depressive-like behavior

Moreau

André

O’Connor

et al. 2008

Brain, Behavior, and Immunity

142

151

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Although cytokine-induced sickness behavior is now well-established, the mechanisms by which chronic inflammation and depression are linked still remain elusive. Therefore this study aimed to develop a suitable model to identify the neurobiological basis of depressive-like behavior induced by chronic inflammation, independently of sickness behavior. We chose to measure the behavioral consequences of chronic inoculation of mice with Bacillus Calmette-Guerin (BCG), which has been shown to chronically activate both lung and brain indoleamine 2,3-dioxygenase (IDO), a tryptophan-catabolizing enzyme that mediates the occurrence of depressive-like behavior following acute innate immune system activation. BCG inoculation induced an acute episode of sickness (approximately 5 days) that was followed by development of delayed depressive-like behaviors lasting over several weeks. Transient body weight loss, reduction of motor activity and the febrile response to BCG were dissociated temporarily from a sustained increase in the duration of immobility in both forced swim and tail suspension tests, reduced voluntary wheel running and decreased preference for sucrose (a test of anhedonia). Moreover, we show that a distinct pattern of cytokine production and IDO activation parallels the transition from sickness to depression. Protracted depressive-like behavior, but not sickness behavior, was associated with sustained increase in plasma interferon-γ and TNF-α concentrations and peripheral IDO activation. Together, these promising new data establish BCG inoculation of mice as a reliable rodent model of chronic inflammation-induced depressive-like behaviors that recapitulate many clinical observations and provide important clues about the neurobiological basis through which cytokines may have an impact on affective behaviors.

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Section: Introductionmentioning

confidence: 99%

Inoculation of Bacillus Calmette-Guerin to mice induces an acute episode of sickness behavior followed by chronic depressive-like behavior

Moreau

André

O’Connor

et al. 2008

Brain, Behavior, and Immunity

142

151

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“…The observed diminished efficacy of BCG vaccination has resulted in intensive research into developing novel TB vaccines that could surpass the efficacy of the current BCG vaccine [6][7][8]. Despite investigations into developing alternatives, BCG remains the gold standard for TB vaccines [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Lactoferrin enhanced efficacy of the BCG vaccine to generate host protective responses against challenge with virulent Mycobacterium tuberculosis

Hwang

Wilk

Budnicka

et al. 2007

Vaccine

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Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is a disease with world wide consequences, affecting nearly a third of the world's population. The established vaccine for TB, an attenuated strain of Mycobacterium bovis Calmette Guerin (BCG), has existed since 1921. Lactoferrin, an iron binding protein found in mucosal secretions and granules of neutrophils was hypothesized to be an ideal adjuvant to enhance the efficacy of the BCG vaccine, specifically because of previous reports of lactoferrin enhancement of IL-12 production from macrophages infected with BCG. Different vaccination protocols were investigated for generation of host protective responses against MTB infection using lactoferrin admixed to the BCG vaccine. Resulting effects demonstrate that BCG/lactoferrin increased host protection against MTB infection by decreasing organ bacterial load and reducing lung histopathology; significant reduction in tissue CFUs and pathology were observed post challenge compared to those seen with BCG alone. Addition of lactoferrin to the vaccine led to reduced pathological damage upon subsequent infection with virulent MTB, with positive results demonstrated when admixed in oil-based vehicle (incomplete Freund's adjuvant; IFA) or when given with BCG in saline. The observed post-challenge results paralleled increasing production of IFN-γ and IL-6, but only limited changes to proinflammatory mediators TNF-α or IL-1β from BCG stimulated splenocytes. Overall, these studies indicate that lactoferrin is a useful and effective adjuvant to improve efficacy of the BCG vaccine, with potential to reduce related tissue damage and pulmonary histopathology.

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“…While BCG has been in use for nearly 85 years, the current vaccine has limited efficacy in controlling MTB infection in adults [5,16]; there are only a small number of experimental vaccine alternatives that surpass the efficacy of the existing BCG vaccine [6]. Successful control of MTB infection relies on mycobacterial antigen-specific cellular immunity; namely, a T cell dominated DTH response that is often characterized by high induction of IFN-γ, an indication of T cell helper type-1 (T H 1) activation [19].…”

Section: Introductionmentioning

confidence: 99%

Lactoferrin modulation of IL-12 and IL-10 response from activated murine leukocytes

Hwang¹,

Wilk²,

Bangale³

et al. 2007

Med Microbiol Immunol

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Lactoferrin possesses a wide range of immunomodulatory activities, including promotion of the delayed type hypersensitivity response (DTH) towards BCG (Bacillus Calmette Guerin) antigens. Addition of Lactoferrin as an adjuvant to the BCG vaccine was previously demonstrated to augment protection against subsequent mycobacterial challenge, with concomitant development of a strong T cell helper type 1 (T H 1) immunity. Because generation of T H 1 immunity is in large part dependent on the balance of monocytic pro-and anti-inflammatory cytokines, the effect of Lactoferrin on leukocytes was investigated. Lactoferrin enhanced proinflammatory responses in a dose-dependant manner from splenocyte and adherent (F4/80 + ) splenocyte populations, bone marrow derived monocytes (BMM), and J774A.1 cultured cells. In all scenarios tested, Lactoferrin induced a strong increase in the ratio of IL-12:IL-10 production from LPS stimulated cells. Examination of Lactoferrin effects on BCG infected J774A.1 cells and on BMM revealed similar immunomodulatory effects, with particularly strong increase in IL-12 production. Furthermore, immunization of mice with BCG admixed with Lactoferrin led to increased generation of CD4+ cells expressing IFN-γ upon restimulation with BCG antigens. These results provide molecular evidence to support the role of Lactoferrin as an adjuvant candidate to augment development of DTH response to vaccine antigens.

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Preventing Tuberculosis with Bacillus Calmette-Guérin Vaccine: A Meta-Analysis of the Literature

Cited by 241 publications

References 22 publications

Inoculation of Bacillus Calmette-Guerin to mice induces an acute episode of sickness behavior followed by chronic depressive-like behavior

Inoculation of Bacillus Calmette-Guerin to mice induces an acute episode of sickness behavior followed by chronic depressive-like behavior

Lactoferrin enhanced efficacy of the BCG vaccine to generate host protective responses against challenge with virulent Mycobacterium tuberculosis

Lactoferrin modulation of IL-12 and IL-10 response from activated murine leukocytes

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