BCG, the only vaccine licensed against tuberculosis, demonstrates variable efficacy in humans. Recent preclinical studies highlight potential for mucosal BCG vaccination to improve protection. Lung tissue-resident memory T cells reside within parenchyma, potentially playing an important role protective immunity tuberculosis. We hypothesised that may enhance generation of lung cells, affording improved protection Mycobacterium In a mouse model, intranasal (IN) conferred superior lungs...

Tuberculosis (TB) remains one of the most important infectious diseases man and animals, only available vaccine (BCG) requires urgent replacement or improvement. To facilitate this, protective mechanisms induced by BCG require further understanding. As a live attenuated vaccine, persistence bacilli in host may be crucial mechanism. We have investigated long term following vaccination influence on immune response protection, using an established murine model. sought to establish whether...

To more closely understand the mechanisms of how BCG vaccination confers immunity would help to rationally design improved tuberculosis vaccines that are urgently required. Given established central role CD4 T cells in induced immunity, we sought characterise generation memory cell responses and M. bovis infection a murine challenge model. We demonstrate single systemic induces distinct mucosal populations effector (T(EM)) vaccinated mice. These CD4+CD44(hi)CD62L(lo)CD27⁻ concomitantly...

Bovine tuberculosis (bTb) remains a major and economically important disease of livestock. Improved ante-mortem diagnostic tools would help to underpin novel control strategies. The definition biomarkers correlating with progression could have impact on the rational design approaches for bTb. We used murine bTb model identify promising candidates in host transcriptome post-infection. RNA from vitro-stimulated splenocytes lung cells BALB/c mice infected aerogenically Mycobacterium bovis were...

It is generally assumed that the inbred mouse strains BALB/c (H-2(d)) and C57BL/6 (H-2(b)) respond to mycobacterial infection with distinct polarisation of T helper responses, predisposed Th1 Th2. We investigated this in a BCG-immunisation, Mycobacterium bovis challenge model. Following immunisation, lung spleen cell cytokine responses vitro re-stimulation cocktail seven secreted, immunogenic, recombinant proteins were determined. In both spleen, cells produced at least 2-fold more IFN-γ, up...

Tuberculosis (TB) is the biggest cause of human mortality from an infectious disease. The only vaccine currently available, bacille Calmette-Guérin (BCG), demonstrates some protection against disseminated disease in childhood but very variable efficacy pulmonary adults. A greater understanding protective host immune responses required order to aid development improved vaccines. Tissue-resident memory T cells (TRM) are a recently-identified subset which may represent important component...

Background In the present study, we applied microarray technology to define biosignatures by transcriptome analysis in lung and spleen samples after BCG vaccination M. bovis infection of BALB/c mice. The aims were two-fold, namely that could predict vaccine success before challenge, biomarker patterns correlated with anamnestic protective responses following exposure virulent bovis. Further, these should be detectable without vitro antigenic challenge. Principal Findings After vaccination,...

The assessment of antigen-specific T cell responses by intracellular cytokine staining (ICS) has become a routine technique in studies vaccination and immunity. Here, we highlight how the duration vitro antigen pre-stimulation, combined with accumulation period, are critical parameters these methods. effect varying upon diversity frequency multifunctional CD4 subsets been investigated using murine model TB cattle naturally infected Mycobacterium bovis. We demonstrate substantial influence...

Abstract Conventional dendritic cells (cDC) are professional antigen-presenting that induce immune activation or tolerance. Two functionally specialised populations, termed cDC1 and cDC2, have been described in humans, mice, ruminants recently pigs. Pigs an important biomedical model species a key source of animal protein; therefore further understanding their system will help underpin the development disease prevention strategies. To characterise cDC populations porcine blood, DC were...

ABSTRACT Tuberculosis (TB) remains one of the most important infectious diseases humans and animals. Mycobacterium bovis BCG, only currently available TB vaccine, demonstrates variable levels efficacy; therefore, a replacement or supplement to BCG is required. Protein subunit vaccines have shown promise but require use adjuvants enhance their immunogenicity. Using protective mycobacterial antigen Rv3019c, we evaluated induction relevant immune responses by adjuvant formulations directly in...

Bovine tuberculosis (bTB) remains a globally significant veterinary health problem. Defining correlates of protection can accelerate the development novel vaccines against TB. As cultured IFNγ ELISPOT (cELISPOT) assay has been shown to predict and duration immunity in vaccinated cattle, we sought characterize phenotype responding T-cells. Using expression CD45RO CD62L purified by cytometric cell sorting four distinct CD4+ populations: CD45RO+CD62Lhi, CD45RO+CD62Llo, CD45RO−CD62Lhi...

Abstract Two strains of mice (BALB/c and CB6F1) were vaccinated with a range Bacille Calmette-Guérin (BCG) Danish doses from 3 × 10 5 to 30 CFU/mouse, followed by aerosol infection Mtb (H37Rv or West-Beijing HN878 strain). The results indicated that both when infected exhibited significant protection in their lungs BCG at —3000 CFU (BALB/c) —300 (CB6F1). Whereas, was seen H37Rv. A increase the frequencies BCG-specific IFNγ + IL2 TNFα CD4 T cells (CB6F1) seen. correlated burden whereas,...

Previous experiments for the identification of novel diagnostic or vaccine candidates bovine tuberculosis have followed a targeted approach, wherein specific groups proteins suspected to contain likely are prioritized immunological assessment (for example, with in silico approaches). However, disadvantage this approach is that sets analyzed restricted by initial selection criteria. In paper, we describe series evaluate nonbiased antigen mining utilizing Gateway clone set Mycobacterium...

Boosting BCG using heterologous prime-boost represents a promising strategy for improved tuberculosis (TB) vaccines, and adenovirus (Ad) delivery is established as an efficacious boosting vehicle. Although studies demonstrate that intranasal administration of Ad boost to offers optimal protection, this not currently possible in cattle. Using vaccine expressing the mycobacterial antigen TB10.4 (BCG/Ad-TB10.4), we demonstrate, parenteral immunised mice induce specific CD8(+) IFN-γ producing T...

Brucellosis is a global disease and the world’s most prevalent zoonosis. All cases in livestock humans are caused by members of genus Brucella that possess surface O-polysaccharide (OPS) comprised rare monosaccharide 4-deoxy-4-formamido-D-mannopyranose assembled with α1,2 α1,3 linkages. The OPS bacterium basis for serodiagnostic tests brucellosis. Bacteria also contain same can induce antibodies cross-react serological tests. In previous work we established synthetic oligosaccharides,...

Abstract Heterologous BCG prime-boost regimens represent a promising strategy for an urgently required improved tuberculosis vaccine. Identifying the mechanisms which underpin enhanced protection induced by such strategies is one key aim would significantly accelerate rational vaccine development. Experimentally, airway vaccination induces greater efficacy than parenteral delivery; in both conventional and heterologous boosting of immunisation. However, effect delivering component prime...

Tuberculosis (TB) remains a global pandemic, in both animals and man, novel vaccines are urgently required. Heterologous prime-boost of BCG represents promising strategy for improved TB vaccines, with respiratory delivery the most efficacious to date. Such an approach may be ideal vaccination against bovine (bTB), but presents technical challenge cattle. Inert bacterial spores represent attractive vaccine vehicle. Therefore we evaluated whether parenterally administered when used as boost...

Abstract In this study, 2 strains of mice (BALB/c and CB6F1) were vaccinated with a range Bacille Calmette-Guérin (BCG) Danish doses from 3×10 5 to 30 CFU/mouse, followed by either immunogenicity evaluation or aerosol infection Mycobacterium tuberculosis (a laboratory strain H37Rv West-Beijing HN878 strain). The results indicated that both when infected exhibited significant protection in their lungs BCG at – 3000 CFU (BALB/c) -300 (CB6F1). Whereas, H37Rv, was seen - 300 CFU. Immunological...