Abstract
BackgroundBacillus ancthracis causes cutaneous, pulmonary, or gastrointestinal forms of anthrax. B. anthracis is a pathogenic bacterium that is potentially to be used in bioterrorism because it can be produced in the form of spores. Currently, protective antigen (PA)-based vaccines are being used for the prevention of anthrax, but it is necessary to develop more safe and effective vaccines due to their prolonged immunization schedules and adverse reactions.MethodsWe selected the lipoprotein GBAA0190, a potent inducer of host immune response, present in anthrax spores as a novel potential vaccine candidate. Then, we evaluated its immune-stimulating activity in the bone marrow-derived macrophages (BMDMs) using enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Protective efficacy of GBAA0190 was evaluated in the guinea pig (GP) model.ResultsThe recombinant GBAA0190 (r0190) protein induced the expression of various inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1α (MIP-1α) in the BMDMs. These immune responses were mediated through toll-like receptor 1/2 via activation of mitogen-activated protein (MAP) kinase and Nuclear factor-κB (NF-κB) pathways. We demonstrated that not only immunization of r0190 alone, but also combined immunization with r0190 and recombinant PA showed significant protective efficacy against B. anthracis spore challenges in the GP model.ConclusionsOur results suggest that r0190 may be a potential target for anthrax vaccine.
Highlights
Bacillus ancthracis causes cutaneous, pulmonary, or gastrointestinal forms of anthrax
The GBAA0190 protein was selected as a vaccine target because it is located on the B. anthracis spores [22] that make initial contacts with the host immune system
To examine whether the GBAA0190 protein is expressed in the B. anthracis spores, proteins were prepared from spores, vegetative cells, and culture supernatants, respectively
Summary
B. anthracis is a pathogenic bacterium that is potentially to be used in bioterrorism because it can be produced in the form of spores. Bacillus anthracis is a Gram-positive, spore-forming, rod-shaped bacterium which causes acute infectious disease anthrax. ET works as a calmodulin-dependent adenylate cyclase that elevates intracellular level of cyclic adenosine monophosphate (cAMP) resulting in a severe change of cellular water balance and producing massive edema [4, 5]. Among these three proteins, PA has been the primary target for developing or licensed anthrax vaccines such as anthrax vaccine adsorbed (AVA) and anthrax vaccine precipitated (AVP) [8]
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