Anti-M. tuberculosis Polyclonal antibody

The continuing emergence of viral pathogens and their rapid spread into heavily populated areas around the world underscore the urgency for development of highly effective vaccines to generate protective antiviral Ab responses. Many established and newly emerging viral pathogens, including HIV and Ebola viruses, are most prevalent in regions of the world in which Mycobacterium tuberculosis infection remains endemic and vaccination at birth with M. bovis bacille Calmette-Guerin (BCG) is widely used. We have investigated the potential for using CD4(+) T cells arising in response to BCG as a source of help for driving Ab responses against viral vaccines. To test this approach, we designed vaccines comprised of protein immunogens fused to an immunodominant CD4(+) T cell epitope of the secreted Ag 85B protein of BCG. Proof-of-concept experiments showed that the presence of BCG-specific Th cells in previously BCG-vaccinated mice had a dose-sparing effect for subsequent vaccination with fusion proteins containing the Ag 85B epitope and consistently induced isotype switching to the IgG2c subclass. Studies using an Ebola virus glycoprotein fused to the Ag 85B epitope showed that prior BCG vaccination promoted high-affinity IgG1 responses that neutralized viral infection. The design of fusion protein vaccines with the ability to recruit BCG-specific CD4(+) Th cells may be a useful and broadly applicable approach to generating improved vaccines against a range of established and newly emergent viral pathogens.

Objectives: Interferons (IFNs) play multifunctional roles in host defense against infectious diseases by inducing IFN-stimulated genes (ISGs). However, little is known about how ISGs regulate host immune response to Mycobacterium tuberculosis (Mtb) infection, the major cause of tuberculosis (TB). Methods: We thus profiled the potential effects and mechanisms of eight Mtb-induced ISGs on Mtb infection by RNA interference in human macrophages (W phi s) derived from peripheral blood monocytes (hMDMs) and THP-1 cell line derived W phi s (THP-1-W phi s). Results: MxA silencing significantly decreased intracellular Mtb infection in M phi s. Mechanistically, MxA silencing promoted inflammatory cytokines IL-1 beta, IL-6 and TNF-alpha production, and induced NF-kappa B p65 activation. Pharmacological inhibition of NF-kappa B p65 activation or gene silencing of NF-kappa B p65 blocked the increased production of IL-1 beta, IL-6 and TNF-alpha and restored Mtb infection by MxA silencing. Furthermore, pharmacological inhibition of TAK1 and IKK alpha/beta blocked NF-kappa B p65 activation and subsequent production of pro-inflammatory cytokines by MxA silencing. Isoniazid (INH) treatment and MxA silencing could promote TAK1-IKK alpha/beta-NF-kappa B signaling pathway activation and combat Mtb infection independently. Conclusions: Our results reveal a novel role of MxA in regulating TAK1-IKK alpha/beta-NF-kappa B signaling activation and production of antimicrobial inflammatory cytokines upon Mtb infection, providing a potential target for clinical treatment of TB. (C) 2020 The British Infection Association. Published by Elsevier Ltd. All rights reserved.