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Joanna R Kirman - One of the best experts on this subject based on the ideXlab platform.
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accelerating the secondary immune response by inactivating cd4 cd25 t regulatory cells prior to BCG Vaccination does not enhance protection against tuberculosis
European Journal of Immunology, 2008Co-Authors: Kylie M Quinn, Fenella J Rich, Lisa M Goldsack, Brett Delahunt, Geofferey W. De Lisle, Bryce M. Buddle, Joanna R KirmanAbstract:CD4+CD25+ natural T regulatory cells (Tregs) have been shown to suppress protective immune responses in several different Vaccination models. Since the effect of Tregs on Vaccination against tuberculosis (Tb) was unknown, we used a murine model to investigate whether natural Tregs suppress the development of protective immunity following Mycobacterium bovis bacille Calmette-Guerin (BCG) Vaccination. Using a monoclonal antibody against CD25, natural Tregs were inactivated prior to Vaccination with BCG. The primary immune response was evaluated after BCG Vaccination and the secondary immune response was assessed after an intranasal BCG challenge 42 days after Vaccination. Inactivation of natural Tregs prior to Vaccination led to an increased immune response 14 days after Vaccination, increased numbers of antigen-responsive lymphocytes immediately prior to secondary challenge and the earlier appearance of IFN-γ-producing CD4+ and CD8+ lymphocytes in the draining lymph nodes and lungs after challenge. Despite this, protection from virulent Mycobacterium tuberculosis or M. bovis aerosol challenge was unaffected by natural Treg inactivation prior to BCG Vaccination. This suggests that increasing the primary and accelerating the secondary immune responses by inactivating natural Tregs at the time of Vaccination, does not affect the development of protective immunity to Tb.
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cover picture accelerating the secondary immune response by inactivating cd4 cd25 t regulatory cells prior to BCG Vaccination does not enhance protection against tuberculosis eur j immunol 3 2008
European Journal of Immunology, 2008Co-Authors: Kylie M Quinn, Fenella J Rich, Lisa M Goldsack, Brett Delahunt, Geofferey W. De Lisle, Bryce M. Buddle, Joanna R KirmanAbstract:The cover shows a lung section taken from mice treated i.p. with PC61 (a mAb to CD25), vaccinated with bacillus Calmette-Guerin (BCG) 3 days later and then challenged with Mycobacterium bovisvia aerosol a further 42 days later. The section is stained with hematoxylin and eosin, and shows that pulmonary inflammation, although present, is limited. The image is taken from Quinn et al. (pp. 695–705) in which the authors demonstrate that inactivation of CD4+CD25+ natural Treg does not influence the development of protective immunity following BCG Vaccination, even though the immune response to mycobacterial antigens early after Vaccination is increased.
Helen Mcshane - One of the best experts on this subject based on the ideXlab platform.
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The Humoral Immune Response to BCG Vaccination.
Frontiers in Immunology, 2019Co-Authors: Rachel Tanner, Bernardo Villarreal-ramos, H. Martin Vordermeier, Helen McshaneAbstract:Bacillus Calmette Guerin (BCG) is the only currently available vaccine against tuberculosis (TB), but it confers incomplete and variable protection against pulmonary TB in humans and bovine TB (bTB) in cattle. Insights into the immune response induced by BCG offer an underexploited opportunity to gain knowledge that may inform the design of a more efficacious vaccine, which is urgently needed to control these major global epidemics. Humoral immunity in TB and bTB has been neglected, but recent studies supporting a role for antibodies in protection against TB has driven a growing interest in determining their relevance to vaccine development. In this manuscript we review what is known about the humoral immune response to BCG Vaccination and re-Vaccination across species, including evidence for the induction of specific B cells and antibodies; and how these may relate to protection from TB or bTB. We discuss potential explanations for often conflicting findings and consider how factors such as BCG strain, manufacturing methodology and route of administration influence the humoral response. As novel Vaccination strategies include BCG prime-boost regimens, the literature regarding off-target immunomodulatory effects of BCG Vaccination on non-specific humoral immunity is also reviewed. Overall, reported outcomes to date are inconsistent, but indicate that humoral responses are heterogeneous and may play different roles in different species, populations, or individual hosts. Further study is warranted to determine whether a new TB vaccine could benefit from the targeting of humoral as well as cell-mediated immunity.
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enhanced protection conferred by mucosal BCG Vaccination associates with presence of antigen specific lung tissue resident pd 1 klrg1 cd4 t cells
Mucosal Immunology, 2019Co-Authors: Naomi C Bull, Elena Stylianou, Daryan A Kaveh, Nawamin Pinpathomrat, Janet Pasricha, Rachel Harringtonkandt, M C Garciapelayo, Philip J Hogarth, Helen McshaneAbstract:BCG, the only vaccine licensed against tuberculosis, demonstrates variable efficacy in humans. Recent preclinical studies highlight the potential for mucosal BCG Vaccination to improve protection. Lung tissue-resident memory T cells reside within the parenchyma, potentially playing an important role in protective immunity to tuberculosis. We hypothesised that mucosal BCG Vaccination may enhance generation of lung tissue-resident T cells, affording improved protection against Mycobacterium tuberculosis. In a mouse model, mucosal intranasal (IN) BCG Vaccination conferred superior protection in the lungs compared to the systemic intradermal (ID) route. Intravascular staining allowed discrimination of lung tissue-resident CD4+ T cells from those in the lung vasculature, revealing that mucosal Vaccination resulted in an increased frequency of antigen-specific tissue-resident CD4+ T cells compared to systemic Vaccination. Tissue-resident CD4+ T cells induced by mucosal BCG displayed enhanced proliferative capacity compared to lung vascular and splenic CD4+ T cells. Only mucosal BCG induced antigen-specific tissue-resident T cells expressing a PD-1+ KLRG1− cell-surface phenotype. These cells constitute a BCG-induced population which may be responsible for the enhanced protection observed with IN Vaccination. We demonstrate that mucosal BCG Vaccination significantly improves protection over systemic BCG and this correlates with a novel population of BCG-induced lung tissue-resident CD4+ T cells.
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using data from macaques to predict gamma interferon responses after mycobacterium bovis BCG Vaccination in humans a proof of concept study of immunostimulation immunodynamic modeling methods
Clinical and Vaccine Immunology, 2017Co-Authors: Sophie J Rhodes, Helen Mcshane, Helen A Fletcher, Thomas G Evans, Gwenan M Knight, Charlotte Sarfas, Andrew D White, Ansar A Pathan, Sally SharpeAbstract:Macaques play a central role in the development of human tuberculosis (TB) vaccines. Immune and challenge responses differ across macaque and human subpopulations. We used novel immunostimulation/immunodynamic modeling methods in a proof-of-concept study to determine which macaque subpopulations best predicted immune responses in different human subpopulations. Data on gamma interferon (IFN-γ)-secreting CD4+ T cells over time after recent Mycobacterium bovis BCG Vaccination were available for 55 humans and 81 macaques. Human population covariates were baseline BCG Vaccination status, time since BCG Vaccination, gender, and the monocyte/lymphocyte cell count ratio. The macaque population covariate was the colony of origin. A two-compartment mathematical model describing the dynamics of the IFN-γ T cell response after BCG Vaccination was calibrated to these data using nonlinear mixed-effects methods. The model was calibrated to macaque and human data separately. The association between subpopulations and the BCG immune response in each species was assessed. The macaque subpopulations that best predicted immune responses in different human subpopulations were identified using Bayesian information criteria. We found that the macaque colony and the human baseline BCG status were significantly (P < 0.05) associated with the BCG-induced immune response. For humans who were BCG naive at baseline, Indonesian cynomolgus macaques and Indian rhesus macaques best predicted the immune response. For humans who had already been BCG vaccinated at baseline, Mauritian cynomolgus macaques best predicted the immune response. This work suggests that the immune responses of different human populations may be best modeled by different macaque colonies, and it demonstrates the potential utility of immunostimulation/immunodynamic modeling to accelerate TB vaccine development.
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the tuberculin skin test tst is affected by recent BCG Vaccination but not by exposure to non tuberculosis mycobacteria ntm during early life
PLOS ONE, 2010Co-Authors: Sarah Burl, Helen Mcshane, Uche J Adetifa, Momodou Cox, Ebrima S Touray, Hilton Whittle, Sarah Rowlandjones, Katie L FlanaganAbstract:The tuberculin skin test (TST) is widely used in TB clinics to aid Mycobacterium tuberculosis (M.tb) diagnosis, but the definition and the significance of a positive test in very young children is still unclear. This study compared the TST in Gambian children at 4½ months of age who either received BCG Vaccination at birth (Group 1) or were BCG naive (Group 2) in order to examine the role of BCG Vaccination and/or exposure to environmental mycobacteria in TST reactivity at this age. Nearly half of the BCG vaccinated children had a positive TST (≥5 mm) whereas all the BCG naive children were non-reactive, confirming that recent BCG Vaccination affects TST reactivity. The BCG naive children demonstrated in vitro PPD responses in peripheral blood in the absence of TST reactivity, supporting exposure to and priming by environmental mycobacterial antigens. Group 2 were then vaccinated at 4½ months of age and a repeat TST was performed at 20–28 months of age. Positive reactivity (≥5 mm) was evident in 11.1% and 12.5% infants from Group 1 and Group 2 respectively suggesting that the timing of BCG Vaccination had little effect by this age. We further assessed for immune correlates in peripheral blood at 4½ months of age. Mycobacterial specific IFNγ responses were greater in TST responders than in non-responders, although the size of induration did not correlate with IFNγ. However the IFNγ: IL-10 ratio positively correlated with TST induration suggesting that the relationship between PPD induced IFNγ and IL-10 in the peripheral blood may be important in controlling TST reactivity. Collectively these data provide further insights into how the TST is regulated in early life, and how a positive response might be interpreted.
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the effect of tuberculin skin test and BCG Vaccination on the expansion of ppd specific ifn γ producing cells ex vivo
Vaccine, 2007Co-Authors: Roger H Brookes, Helen Mcshane, Philip C Hill, Patrick K Owiafe, Hannah B Ibanga, Simon Donkor, Timothy Awine, Richard A AdegbolaAbstract:Understanding the immunogenicity of BCG in a population where it has failed will facilitate the design of new TB vaccines. We assessed the immunogenicity of M. bovis BCG over 12 months by ELISPOT assay. Forty-one adolescents and young Gambian male adults received a tuberculin skin test (TST) which was followed one week later by BCG Vaccination, but the 23 control subjects received neither of these. TST alone significantly induced PPD-specific IFN-γ producing cells. Twenty-three percent of subjects did not respond to BCG, which was associated with higher pre-existing ex vivo response to PPD. Paradoxically, amongst BCG responders there was a correlation between pre-existing response and subsequent response to BCG. We conclude that BCG is immunogenic, but this effector response is short-lived and can be limited in higher pre-existing anti-mycobacterial immunity, suggesting a possible threshold beyond which BCG immunogenicity is inhibited.
Kylie M Quinn - One of the best experts on this subject based on the ideXlab platform.
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accelerating the secondary immune response by inactivating cd4 cd25 t regulatory cells prior to BCG Vaccination does not enhance protection against tuberculosis
European Journal of Immunology, 2008Co-Authors: Kylie M Quinn, Fenella J Rich, Lisa M Goldsack, Brett Delahunt, Geofferey W. De Lisle, Bryce M. Buddle, Joanna R KirmanAbstract:CD4+CD25+ natural T regulatory cells (Tregs) have been shown to suppress protective immune responses in several different Vaccination models. Since the effect of Tregs on Vaccination against tuberculosis (Tb) was unknown, we used a murine model to investigate whether natural Tregs suppress the development of protective immunity following Mycobacterium bovis bacille Calmette-Guerin (BCG) Vaccination. Using a monoclonal antibody against CD25, natural Tregs were inactivated prior to Vaccination with BCG. The primary immune response was evaluated after BCG Vaccination and the secondary immune response was assessed after an intranasal BCG challenge 42 days after Vaccination. Inactivation of natural Tregs prior to Vaccination led to an increased immune response 14 days after Vaccination, increased numbers of antigen-responsive lymphocytes immediately prior to secondary challenge and the earlier appearance of IFN-γ-producing CD4+ and CD8+ lymphocytes in the draining lymph nodes and lungs after challenge. Despite this, protection from virulent Mycobacterium tuberculosis or M. bovis aerosol challenge was unaffected by natural Treg inactivation prior to BCG Vaccination. This suggests that increasing the primary and accelerating the secondary immune responses by inactivating natural Tregs at the time of Vaccination, does not affect the development of protective immunity to Tb.
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cover picture accelerating the secondary immune response by inactivating cd4 cd25 t regulatory cells prior to BCG Vaccination does not enhance protection against tuberculosis eur j immunol 3 2008
European Journal of Immunology, 2008Co-Authors: Kylie M Quinn, Fenella J Rich, Lisa M Goldsack, Brett Delahunt, Geofferey W. De Lisle, Bryce M. Buddle, Joanna R KirmanAbstract:The cover shows a lung section taken from mice treated i.p. with PC61 (a mAb to CD25), vaccinated with bacillus Calmette-Guerin (BCG) 3 days later and then challenged with Mycobacterium bovisvia aerosol a further 42 days later. The section is stained with hematoxylin and eosin, and shows that pulmonary inflammation, although present, is limited. The image is taken from Quinn et al. (pp. 695–705) in which the authors demonstrate that inactivation of CD4+CD25+ natural Treg does not influence the development of protective immunity following BCG Vaccination, even though the immune response to mycobacterial antigens early after Vaccination is increased.
Nigel Curtis - One of the best experts on this subject based on the ideXlab platform.
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does BCG Vaccination protect against nontuberculous mycobacterial infection a systematic review and meta analysis
The Journal of Infectious Diseases, 2018Co-Authors: Petra Zimmermann, Adam Finn, Nigel CurtisAbstract:Background The incidence of nontuberculous mycobacterial (NTM) infections is increasing worldwide, particularly NTM lymphadenitis and skin infections (Buruli ulcer). This review summarizes the evidence for the protective effectiveness of BCG Vaccination against NTM disease. Methods A systematic search using PRISMA guidelines was done for controlled studies investigating the protective effectiveness of BCG Vaccination against NTM disease in immunocompetent individuals. This revealed 10 studies, including almost 12 million participants. Results Three cohort studies in industrialized countries suggest that the incidence of NTM lymphadenitis is greatly reduced among BCG-vaccinated children compared with BCG-unvaccinated children, with a risk ratio (RR) of 0.04 (95% confidence interval [CI], .01-.21). In two randomized trials in low-income countries, BCG protected against Buruli ulcer for the first 12 months following Vaccination (RR, 0.50 [95% CI, .37-.69]). Four case-control studies had conflicting results. One cohort study found that individuals with Buruli ulcer are less likely to develop osteomyelitis if they have a BCG scar (RR, 0.36 [95% CI, .22-.58]). No studies have compared different BCG vaccine strains or the effect of reVaccination in this setting. Conclusions The protective effect of BCG Vaccination against NTM should be taken into consideration when deciding on recommendations for discontinuation of universal BCG Vaccination programs and in assessing new vaccines designed to replace BCG.
Bryce M. Buddle - One of the best experts on this subject based on the ideXlab platform.
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accelerating the secondary immune response by inactivating cd4 cd25 t regulatory cells prior to BCG Vaccination does not enhance protection against tuberculosis
European Journal of Immunology, 2008Co-Authors: Kylie M Quinn, Fenella J Rich, Lisa M Goldsack, Brett Delahunt, Geofferey W. De Lisle, Bryce M. Buddle, Joanna R KirmanAbstract:CD4+CD25+ natural T regulatory cells (Tregs) have been shown to suppress protective immune responses in several different Vaccination models. Since the effect of Tregs on Vaccination against tuberculosis (Tb) was unknown, we used a murine model to investigate whether natural Tregs suppress the development of protective immunity following Mycobacterium bovis bacille Calmette-Guerin (BCG) Vaccination. Using a monoclonal antibody against CD25, natural Tregs were inactivated prior to Vaccination with BCG. The primary immune response was evaluated after BCG Vaccination and the secondary immune response was assessed after an intranasal BCG challenge 42 days after Vaccination. Inactivation of natural Tregs prior to Vaccination led to an increased immune response 14 days after Vaccination, increased numbers of antigen-responsive lymphocytes immediately prior to secondary challenge and the earlier appearance of IFN-γ-producing CD4+ and CD8+ lymphocytes in the draining lymph nodes and lungs after challenge. Despite this, protection from virulent Mycobacterium tuberculosis or M. bovis aerosol challenge was unaffected by natural Treg inactivation prior to BCG Vaccination. This suggests that increasing the primary and accelerating the secondary immune responses by inactivating natural Tregs at the time of Vaccination, does not affect the development of protective immunity to Tb.
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cover picture accelerating the secondary immune response by inactivating cd4 cd25 t regulatory cells prior to BCG Vaccination does not enhance protection against tuberculosis eur j immunol 3 2008
European Journal of Immunology, 2008Co-Authors: Kylie M Quinn, Fenella J Rich, Lisa M Goldsack, Brett Delahunt, Geofferey W. De Lisle, Bryce M. Buddle, Joanna R KirmanAbstract:The cover shows a lung section taken from mice treated i.p. with PC61 (a mAb to CD25), vaccinated with bacillus Calmette-Guerin (BCG) 3 days later and then challenged with Mycobacterium bovisvia aerosol a further 42 days later. The section is stained with hematoxylin and eosin, and shows that pulmonary inflammation, although present, is limited. The image is taken from Quinn et al. (pp. 695–705) in which the authors demonstrate that inactivation of CD4+CD25+ natural Treg does not influence the development of protective immunity following BCG Vaccination, even though the immune response to mycobacterial antigens early after Vaccination is increased.