Enhanced immunisation and expression strategies using bacterial spores as heat-stable vaccine delivery vehicles

Uyen, Nguyen Q.; Hong, Huynh A.; Cutting, Simon M.

doi:10.1016/j.vaccine.2006.07.025

Cited by 38 publications

(32 citation statements)

References 25 publications

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“…For this purpose, mice were immunized by the sublingual route with recombinant spores of the LDV704 and LDV702 strains. For this step, we used the sublingual immunization route because previous results from our group and others have demonstrated that this administration route is safe and particularly efficient for inducing antigen-specific IgG responses (42,43,45). The results demonstrated that mice immunized with spores of the LDV704 and LDV702 strains developed high anti-P1 IgG responses (445 and 249 g/ml, respectively) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Gut Adhesive Bacillus subtilis Spores as a Platform for Mucosal Delivery of Antigens

et al. 2014

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Bacterial carriers for the mucosal delivery of antigens, particularly those capable of colonizing or invading through the mucosal epithelia, have been intensively investigated (1). Live bacterial vectors can be generated with attenuated pathogens, such as Salmonella and Listeria, or nonpathogenic commensal species, such as Lactococcus and Lactobacillus. Bacteria in the former group of are capable of inducing strong and long-lasting immune responses to passenger antigens but present serious safety concerns, whereas bacteria in the latter group are safer but typically induce much lower immune responses to the passenger antigens (1-3). As a safe nonpathogenic live bacterial vector, Bacillus subtilis, a spore-forming soil Gram-positive bacterial species, has been engineered to express antigens as either vegetative cells or spores (4, 5). As antigen carriers, B. subtilis spores have several attractive features, including a safe record of human and animal use as both probiotic and food additives, remarkable heat resistance, and rather easy genetic and bacteriological manipulation.Currently, two major genetic approaches have been proposed to generate recombinant B. subtilis spores as vaccine delivery vectors. The first approach relies on the expression of a heterologous protein genetically fused to surface-exposed spore coat proteins, such as CotB, CotC, or CotG (6, 7). Such a strategy would allow a better presentation of the passenger antigen to the mucosa-associated lymphoid tissue (MALT) afferent sites, leading to the induction of adaptive immune responses, such as mucosal secretory (IgA) or systemic (IgG) antigen-specific antibody responses (6-8). The second approach is based on a distinct rationale and has employed episomal vectors in which the target antigen is expressed under the control of a promoter (PgsiB) active only at the vegetative cell stage, which means immediately after spore germination (9-11). This antigen delivery approach relies on the fact that B. subtilis spores germinate during transit through the gastrointestinal tract and produce the target antigen at the intestinal lumen or inside the phagocytes of antigen-presenting cells (APCs), leading to the induction of antibody responses in the serum (IgG) and mucosa (fecal IgA) (9-11).However, in both cases, the administration of recombinant spores via mucosal routes typically confers immune responses to the passenger antigen lower than those achieved with delivery systems based on attenuated bacterial strains capable of colonizing the mammalian gastrointestinal tract. The reduced mucosal adjuvant effects of B. subtilis spores have been attributed to several factors, such as a previously established immunity generated by the frequent ingestion of spores, the reduced amount of expressed antigens, and the rapid transit through the gastrointestinal tract, which reduces the chances of a productive interaction with the gut-associated lymphoid tissue (GALT), such as M cells and APCs at Peyer's patches (PPs) (12, 13).In an attempt to improve the performance o...

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Section: Resultsmentioning

confidence: 99%

Gut Adhesive Bacillus subtilis Spores as a Platform for Mucosal Delivery of Antigens

et al. 2014

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“…Authors of many publication presenting B. subtilis spores as a platform for generation of vaccine candidates state that such constructs are heat stable and can prevent degradation of antigen in the stomach environment [4,[14][15][16]. However, none of the authors present experiments showing the direct effect of heat or peptidase treatment of recombinant spores and influence on the antigen content.…”

Section: Resultsmentioning

confidence: 99%

Bacillus subtilis Spore Surface Display System Protects Recombinant Proteins from Degradation-Verified Hypothesis

AAAAga¹,

Weiher²,

Paszkiewicz³

et al. 2017

J Biotechnol Biomater

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Endospores of Bacillus subtilis have been used extensively as a platform for recombinant protein display for nearly two decades. Main use of the spore surface display system is generation of oral vaccines against many human and animal pathogens. Formulation of oral vaccine based on spores is an attractive approach to alternative vaccination due to the timesaving and relative easiness of production. Another advantage of such formulation is stability of presented antigens. It is assumed that the spore coat structure prevents degradation of displayed proteins by many destructive factors such as heat, proteases or stomach environment. However, there is little scientific background and substantial lack of experiments verifying this statement. In our work, we tested protective properties of spores against degradation of displayed antigens in harsh environment. We constructed B. subtilis strains producing spores presenting highly conserved long α-helix (LAH) region of the influenza A virus hemagglutinin. The constructs were obtained by fusion of LAH antigen to protein CotB or CotZ from the spore coat. We treated recombinant spores with destructive agents such as heat, protease, low pH and high-energy irradiation to test protective features of the spore coat. After treatment, spore coat extracts were analyzed by western blot to study fate of the displayed antigen. Results that we publish indicate that spore coat protects displayed antigen from degradation. This work is a strong support of hypothesis stating protective properties of spore surface display system against antigen degradation.

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“…Although natural influenza infection does not result in a robust immune response to this peptide sequence, tricking the animal into producing a robust response has resulted in protective immunity in several animal species (Neirynck et al, 1999;Mozdzanowska et al, 2003;Fiers et al, 2004;Zou et al, 2004). In recent years, the rapid increase in molecular biological techniques has led to the development of more sophisticated vaccines, of which live recombinant bacterial vectored vaccines are one of the most promising (Ashby et al, 2005;Zhang et al, 2006;Duc et al, 2007;Kajikawa et al, 2007;Uyen et al, 2007;Yang et al, 2007;Huang et al, 2008;Liu et al, 2008;Ceragioli et al, 2009;Deguchi et al, 2009). This type of vaccine uses a genetically modified bacterium to express a heterologous antigen.…”

Section: Vaccination For Control Of Salmonella In Poultrymentioning

confidence: 99%

Alternative Strategies for Salmonella Control in Poultry

Téllez¹,

Bielke²,

Hargis³

2012

Salmonella - A Dangerous Foodborne Pathogen

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Enhanced immunisation and expression strategies using bacterial spores as heat-stable vaccine delivery vehicles

Cited by 38 publications

References 25 publications

Gut Adhesive Bacillus subtilis Spores as a Platform for Mucosal Delivery of Antigens

Gut Adhesive Bacillus subtilis Spores as a Platform for Mucosal Delivery of Antigens

Bacillus subtilis Spore Surface Display System Protects Recombinant Proteins from Degradation-Verified Hypothesis

Alternative Strategies for Salmonella Control in Poultry

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