Oral immunization using live Lactococcus lactis co-expressing LACK and IL-12 protects BALB/c mice against Leishmania major infection

Hugentobler, F; Roberto, Raphaël B. Di; Gillard, Joshua; Cousineau, Benoit

doi:10.1016/j.vaccine.2012.07.004

Cited by 35 publications

(22 citation statements)

References 30 publications

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“…Hugentobler and colleagues have engineered L. lactis strains expressing the Leishmania major antigen LACK in the cytoplasm, in a secreted form or with a cell wall anchor, with or without concomitant IL-12 secretion. After oral administration, only the strain secreting the antigen and co-expressing IL-12 induced protection against the parasite [105]. In another study these same authors showed that subcutaneous co-administration of L. lactis secreting IL-12 with either a strain secreting LACK or a strain with a cell wall anchored (CWA)-LACK led to induction of protective immunity [106].…”

Section: Lab Displaying Antigensmentioning

confidence: 97%

Display of recombinant proteins at the surface of lactic acid bacteria: strategies and applications

et al. 2016

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Lactic acid bacteria (LAB) are promising vectors of choice to deliver active molecules to mucosal tissues. They are recognized as safe by the World Health Organization and some strains have probiotic properties. The wide range of potential applications of LAB-driven mucosal delivery includes control of inflammatory bowel disease, vaccine delivery, and management of auto-immune diseases. Because of this potential, strategies for the display of proteins at the surface of LAB are gaining interest. To display a protein at the surface of LAB, a signal peptide and an anchor domain are necessary. The recombinant protein can be attached to the membrane layer, using a transmembrane anchor or a lipoprotein-anchor, or to the cell wall, by a covalent link using sortase mediated anchoring via the LPXTG motif, or by non-covalent liaisons employing binding domains such as LysM or WxL. Both the stability and functionality of the displayed proteins will be affected by the kind of anchor used. The most commonly surfaced exposed recombinant proteins produced in LAB are antigens and antibodies and the most commonly used LAB are lactococci and lactobacilli. Although it is not necessarily so that surface-display is the preferred localization in all cases, it has been shown that for certain applications, such as delivery of the human papillomavirus E7 antigen, surface-display elicits better biological responses, compared to cytosolic expression or secretion. Recent developments include the display of peptides and proteins targeting host cell receptors, for the purpose of enhancing the interactions between LAB and host. Surface-display technologies have other potential applications, such as degradation of biomass, which is of importance for some potential industrial applications of LAB.

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Section: Lab Displaying Antigensmentioning

confidence: 97%

Display of recombinant proteins at the surface of lactic acid bacteria: strategies and applications

et al. 2016

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“…It serves as a starter culture for the production of a variety of cheeses, as well as other dairy products such as sour cream and buttermilk. Owing to the long history of safe consumption and the availability of molecular tools, lactococci have a great potential as mucosal delivery vehicles for therapeutic and prophylactic molecules (Bermudez-Humaran et al 2011; Hugentobler et al 2012; del Carmen et al 2013; Szatraj et al 2014; Kasarełło et al 2016). The ability of L. lactis to adhere to the intestinal mucosa can potentially prolong the contact with the host, and therefore favour its persistence in the gut.…”

Section: Introductionmentioning

confidence: 99%

Contribution of plasmid-encoded peptidase S8 (PrtP) to adhesion and transit in the gut of Lactococcus lactis IBB477 strain

Radziwill-Bienkowska

Robert

Drabot

et al. 2017

Appl Microbiol Biotechnol

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The ability of Lactococcus lactis to adhere to the intestinal mucosa can potentially prolong the contact with the host, and therefore favour its persistence in the gut. In the present study, the contribution of plasmid-encoded factors to the adhesive and transit properties of the L. lactis subsp. cremoris IBB477 strain was investigated. Plasmid-cured derivatives as well as deletion mutants were obtained and analysed. Adhesion tests were performed using non-coated polystyrene plates, plates coated with mucin or fibronectin and mucus-secreting HT29-MTX intestinal epithelial cells. The results indicate that two plasmids, pIBB477a and b, are involved in adhesion of the IBB477 strain. One of the genes localised on plasmid pIBB477b (AJ89_14230), which encodes cell wall-associated peptidase S8 (PrtP), mediates adhesion of the IBB477 strain to bare, mucin- and fibronectin-coated polystyrene, as well as to HT29-MTX cells. Interactions between bacteria and mucus secreted by HT29-MTX cells were further investigated by fluorescent staining and confocal microscopy. Confocal images showed that IBB477 forms dense clusters embedded in secreted mucus. Finally, the ability of IBB477 strain and its ΔprtP deletion mutant to colonise the gastrointestinal tract of conventional C57Bl/6 mice was determined. Both strains were present in the gut for up to 72 h. In summary, adhesion and persistence of IBB477 were analysed by in vitro and in vivo approaches, respectively. Our studies revealed that plasmidic genes encoding cell surface proteins are more involved in the adhesion of IBB477 strain than in the ability to confer a selective advantage in the gut.

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“…In another study of this group it was shown, using LACK- and IL-12-expressing L. lactis , that subcutaneous immunization against L. major infection delays footpad swelling, indicating the necessity for co-administration of L. lactis /sec IL-12 (secreting IL-12) as a Th1-inducing adjuvant (63). Again in another study, the same group showed that if live L. lactis secreting both LACK and IL-12 was used, oral immunization was the only regimen that could protect BALB/c mice partially against L. major infection (62). The L. lactis line generated in these studies provides an attractive cornerstone for further research on live-based vaccines against leishmaniasis and other pathogens.…”

Section: Live Non-pathogenic Vaccinesmentioning

confidence: 99%

Live Vaccination Tactics: Possible Approaches for Controlling Visceral Leishmaniasis

2014

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Vaccination with durable immunity is the main goal and fundamental to control leishmaniasis. To stimulate the immune response, small numbers of parasites are necessary to be presented in the mammalian host. Similar to natural course of infection, strategy using live vaccine is more attractive when compared to other approaches. Live vaccines present the whole spectrum of antigens to the host immune system in the absence of any adjuvant. Leishmanization was the first effort for live vaccination and currently used in a few countries against cutaneous leishmaniasis, in spite of their obstacle and safety. Then, live attenuated vaccines developed with similar promotion of creating long-term immunity in the host with lower side effect. Different examples of attenuated strains are generated through long-term in vitro culturing, culturing under drug pressure, temperature sensitivity, and chemical mutagenesis, but none is safe enough and their revision to virulent form is possible. Attenuation through genetic manipulation and disruption of virulence factors or essential enzymes for intracellular survival are among other approaches that are intensively under study. Other designs to develop live vaccines for visceral form of leishmaniasis are utilization of live avirulent microorganisms such as Lactococcus lactis, Salmonella enterica, and Leishmania tarentolae called as vectored vaccine. Apparently, these vaccines are intrinsically safer and can harbor the candidate antigens in their genome through different genetic manipulation and create more potential to control Leishmania parasite as an intracellular pathogen.

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Oral immunization using live Lactococcus lactis co-expressing LACK and IL-12 protects BALB/c mice against Leishmania major infection

Cited by 35 publications

References 30 publications

Display of recombinant proteins at the surface of lactic acid bacteria: strategies and applications

Display of recombinant proteins at the surface of lactic acid bacteria: strategies and applications

Contribution of plasmid-encoded peptidase S8 (PrtP) to adhesion and transit in the gut of Lactococcus lactis IBB477 strain

Live Vaccination Tactics: Possible Approaches for Controlling Visceral Leishmaniasis

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