Bacillus subtilis

Abstract

Most pathogens enter the body through mucosal surfaces. Mucosal immunization, a non-invasive needle-free route, often stimulates a mucosal immune response that is both effective against mucosal and systemic pathogens. The development of mucosally administered heat-stable vaccines with long shelf life would therefore significantly enhance immunization programs in developing countries by avoiding the need for a cold chain or systemic injections. Currently, recombinant vaccine carriers are being used for antigen delivery. Engineering Bacillus subtilis for use as a non-invasive and heat stable antigen delivery system has proven successful. Bacterial spores protected by multiple layers of protein are known to be robust and resistant to desiccation. Stable constructs have been created by integration into the bacterial chromosome of immunogens. The spore coat has been used as a vehicle for heterologous antigen presentation and protective immunization. Sublingual (SL) and intranasal (IN) routes have recently received attention as delivery routes for therapeutic drugs and vaccines and recent attempts by several investigators, including our group, to develop vaccines that can be delivered intranasally and sublingually have met with a lot of success.As discussed in this review, the use of Bacillus subtilis to express antigens that can be administered either intranasally or sublingually is providing new insights in the area of mucosal vaccines. In our work, we evaluated the efficacy of SL and IN immunizations with B. subtilis engineered to express tetanus toxin fragment C (TTFC) in mice and piglets. These bacteria engineered to express heterologous antigen either on the spore surface or within the vegetative cell have been used for oral, IN and SL delivery of antigens. A Bacillus subtilis spore coat protein, CotC was used as a fusion partner to express the tetanus fragment C. B. subtilis spores known to be highly stable and safe are also easy to purify making this spore-based display system a potentially powerful approach for surface expression of antigens. These advances will help to accelerate the development and testing of new mucosal vaccines against many human and animal diseases.

The immunological characteristics and probiotic function of recombinant Bacillus subtilis spore expressing Clonorchis sinensis cysteine protease

“…First, spore-forming B. subtilis is a non-pathogenic and non-invasive aerobic Gram-positive bacterium [8, 9]. Spores of various Bacillus species are currently being used as probiotics and food supplements in both humans and animals [9, 10].…”

“…First, spore-forming B. subtilis is a non-pathogenic and non-invasive aerobic Gram-positive bacterium [8, 9]. Spores of various Bacillus species are currently being used as probiotics and food supplements in both humans and animals [9, 10]. They can survive under extreme temperature, desiccation, pH and exposure to noxious chemicals and solvents [11, 12].…”

Comparative Analysis of Bacillus subtilis Spores and Monophosphoryl Lipid A as Adjuvants of Protein-Based Mycobacterium tuberculosis-Based Vaccines: Partial Requirement for Interleukin-17A for Induction of Protective Immunity

“…Based on previous studies, spores used as adjuvants were shown to increase antibody and T cell responses to a coadministered soluble antigen (Ag), including both antigen-specific CD4 ϩ and CD8 ϩ T cell responses, as well as complement-and non-complement-fixing antibody isotypes (13). Thus, we hypothesized that B. subtilis spores could function as an adjuvant for the development of a protective immune response to infection with M. tuberculosis.…”

Oral Administration of Bacillus subtilis Endospores Displaying Influenza Virus Matrix Protein 1 Elicit Cellular Immune Response in Mice

“…Influenza virusspecific Cytotoxic T Lymphocytes (CTLs) have been shown in animal studies to limit influenza A virus replication and to protect against lethal influenza A virus challenge [3]. In last year's a new live antigen carrier system emerged [4]. Recent studies show that recombinant endospores of Bacillus subtilis can serve as antigen carriers by fusing peptide of interest to spore coat proteins [5].…”