Bacterium-like particles derived from probiotics: progress, challenges and prospects

Zhou, Xinyao; Gao, Mingchun; De, Xinqi; Sun, Tong; Bai, Zhikun; Luo, Jilong; Wang, Fang; Ge, Junwei

doi:10.3389/fimmu.2023.1263586

Cited by 4 publications

(1 citation statement)

References 104 publications

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“…There is a need to expand the range of mucosal vaccines based on BLP because there are currently few available due to the high technical requirements. BLPs obtained from different immunomodulatory LABs have different adjuvant capacities when used as vaccine adjuvants ( Raya Tonetti et al, 2020 ), but most of the existing studies on BLPs are prepared from Lactococcus lactis , only a few studies have used the probiotic Levilactobacillus to prepare BLP ( Zhou et al, 2023 ). BLPs need an anchoring domain to anchor the antigens to their surface.…”

Section: Introductionmentioning

confidence: 99%

A novel bacterium-like particles platform displaying antigens by new anchoring proteins induces efficacious immune responses

Niu,

Gao,

Ren

et al. 2024

Front. Microbiol.

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Bacterium-like particles (BLP) are the peptidoglycan skeleton particles of lactic acid bacteria, which have high safety, mucosal delivery efficiency, and adjuvant effect. It has been widely used in recent years in the development of vaccines. Existing anchoring proteins for BLP surfaces are few in number, so screening and characterization of new anchoring proteins are necessary. In this research, we created the OACD (C-terminal domain of Escherichia coli outer membrane protein A) to serve as an anchoring protein on the surface of BLP produced by the immunomodulatory bacteria Levilactobacillus brevis 23017. We used red fluorescent protein (RFP) to demonstrate the novel surface display system’s effectiveness, stability, and ability to be adapted to a wide range of lactic acid bacteria. Furthermore, this study employed this surface display method to develop a novel vaccine (called COB17) by using the multi-epitope antigen of Clostridium perfringens as the model antigen. The vaccine can induce more than 50% protection rate against C. perfringens type A challenge in mice immunized with a single dose and has been tested through three routes. The vaccine yields protection rates of 75% for subcutaneous, 50% for intranasal, and 75% for oral immunization. Additionally, it elicits a strong mucosal immune response, markedly increasing levels of specific IgG, high-affinity IgG, specific IgA, and SIgA antibodies. Additionally, we used protein anchors (PA) and OACD simultaneous to show several antigens on the BLP surface. The discovery of novel BLP anchoring proteins may expand the possibilities for creating mucosal immunity subunit vaccines. Additionally, it may work in concert with PA to provide concepts for the creation of multivalent or multiple vaccines that may be used in clinical practice to treat complex illnesses.

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Section: Introductionmentioning

confidence: 99%

A novel bacterium-like particles platform displaying antigens by new anchoring proteins induces efficacious immune responses

Niu,

Gao,

Ren

et al. 2024

Front. Microbiol.

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Proof of concept in utilizing the peptidoglycan skeleton of pathogenic bacteria as antigen delivery platform for enhanced immune response

Jia,

Liu,

Chang

et al. 2024

International Journal of Biological Macromolecules

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A novel oral vaccine delivery system for enhancing stability and immune protection: bacterium-like particle with functional coating

De,

Gao,

Jia

et al. 2024

Front. Microbiol.

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Bacterium-like particles (BLPs) have gained significant attention in vaccine development due to their potential as effective immune enhancers and antigen delivery systems. BLPs are generated by boiling lactic acid bacteria in an acidic solution and are devoid of proteins and nucleic acids, offering advantages in terms of ease of preparation, high safety, and good stability. Furthermore, by employing protein anchor (PA), heterogeneous antigens can be efficiently displayed on the surface of BLPs, resulting in enhanced delivery effectiveness. Despite these benefits, most BLP-based vaccines are currently administered via injection or intranasal delivery, with oral delivery remaining limited. This limitation is primarily due to the harsh environment of the gastrointestinal tract, which degrades the antigens displayed on the surface of these particles. To enhance the efficacy of oral immunization with subunit vaccines, we developed a simple and rapid method for self-assembling a lipid membrane onto the surface of BLPs vaccines, achieving an encapsulation efficiency of up to 99%, and the combination has good biosafety. The novel oral delivery system not only preserves the adjuvant activity of BLPs but also efficiently protects antigens from adverse gastrointestinal environments, increasing the absorption of the vaccine in intestinal Peyer’s patches (PPs). Oral immunization was required only once, and protection after the challenge was up to 100%. Furthermore, we observed rapid immunity and cross-protection. Transcriptome analysis of the small intestine suggested that immune enhancement probably be exerted by promoting the absorption and transport of antigens. Therefore, we posit that the design of this new oral delivery system presents a novel approach to advancing the development of oral subunit vaccines.

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Bacterium-like particles derived from probiotics: progress, challenges and prospects

Cited by 4 publications

References 104 publications

A novel bacterium-like particles platform displaying antigens by new anchoring proteins induces efficacious immune responses

A novel bacterium-like particles platform displaying antigens by new anchoring proteins induces efficacious immune responses

Proof of concept in utilizing the peptidoglycan skeleton of pathogenic bacteria as antigen delivery platform for enhanced immune response

A novel oral vaccine delivery system for enhancing stability and immune protection: bacterium-like particle with functional coating

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