Oral immunization with recombinant<i>Lactococcus lactis</i>delivering a multi-epitope antigen CTB-UE attenuates<i>Helicobacter pylori</i>infection in mice

Li, Xinyang; Xing, Yingying; Guo, Le; Lv, Xiaobo; Song, Hui; Xi, Tao

doi:10.1111/2049-632x.12173

Cited by 40 publications

(24 citation statements)

References 34 publications

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“…For this reason, different routes of administration were examined. For example, in the case of S. pneumoniae , the efficacy of intranasally administered vaccines was evaluated (Hanniffy et al 2007 ), whereas in the case of Helicobacter pylori , oral or intragastric vaccines were the first to be analyzed (Li et al 2014 ). Because the mucosa-associated lymphoid tissue (MALT) mucous-membrane immune system constitutes one network covering the whole body, and because lymphocytes are able to migrate, oral immunization also provides systemic immunity expressed by the mucous membranes of other organs.…”

Section: Lab As Carriers Of Heterologous Bacterial Parasitic and VImentioning

confidence: 99%

Lactic acid bacteria—20 years exploring their potential as live vectors for mucosal vaccination

Wyszyńska

Kobierecka

Bardowski

et al. 2015

Appl Microbiol Biotechnol

121

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Lactic acid bacteria (LAB) are a diverse group of Gram-positive, nonsporulating, low G + C content bacteria. Many of them have been given generally regarded as safe status. Over the past two decades, intensive genetic and molecular research carried out on LAB, mainly Lactococcus lactis and some species of the Lactobacillus genus, has revealed new, potential biomedical LAB applications, including the use of LAB as adjuvants, immunostimulators, or therapeutic drug delivery systems, or as factories to produce therapeutic molecules. LAB enable immunization via the mucosal route, which increases effectiveness against pathogens that use the mucosa as the major route of entry into the human body. In this review, we concentrate on the encouraging application of Lactococcus and Lactobacillus genera for the development of live mucosal vaccines. First, we present the progress that has recently been made in the field of developing tools for LAB genetic manipulations, which has resulted in the successful expression of many bacterial, parasitic, and viral antigens in LAB strains. Next, we discuss the factors influencing the efficacy of the constructed vaccine prototypes that have been tested in various animal models. Apart from the research focused on an application of live LABs as carriers of foreign antigens, a lot of work has been recently done on the potential usage of nonliving, nonrecombinant L. lactis designated as Gram-positive enhancer matrix (GEM), as a delivery system for mucosal vaccination. The advantages and disadvantages of both strategies are also presented.

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Section: Lab As Carriers Of Heterologous Bacterial Parasitic and VImentioning

confidence: 99%

Lactic acid bacteria—20 years exploring their potential as live vectors for mucosal vaccination

Wyszyńska

Kobierecka

Bardowski

et al. 2015

Appl Microbiol Biotechnol

121

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“…In this sense, poor immune responses reported by some groups using live L . lactis have been attributed to the low amount of the expressed antigen in this system [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Rotavirus VP6 protein mucosally delivered by cell wall-derived particles from Lactococcus lactis induces protection against infection in a murine model

Temprana¹,

Argüelles²,

Gutierrez³

et al. 2018

PLoS ONE

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Rotaviruses are the primary cause of acute gastroenteritis in children worldwide. Although the implementation of live attenuated vaccines has reduced the number of rotavirus-associated deaths, variance in their effectiveness has been reported in different countries. This fact, among other concerns, leads to continuous efforts for the development of new generation of vaccines against rotavirus.In this work, we describe the obtention of cell wall-derived particles from a recombinant Lactococcus lactis expressing a cell wall-anchored version of the rotavirus VP6 protein. After confirming by SDS-PAGE, Western blot, flow cytometry and electronic immunomicroscopy that these particles were carrying the VP6 protein, their immunogenic potential was evaluated in adult BALB/c mice. For that, mucosal immunizations (oral or intranasal), with or without the dmLT [(double mutant Escherichia coli heat labile toxin LT(R192G/L211A)] adjuvant were performed. The results showed that these cell wall-derived particles were able to generate anti-rotavirus IgG and IgA antibodies only when administered intranasally, whether the adjuvant was present or not. However, the presence of dmLT was necessary to confer protection against rotavirus infection, which was evidenced by a 79.5 percent viral shedding reduction.In summary, this work describes the production of cell wall-derived particles which were able to induce a protective immune response after intranasal immunization. Further studies are needed to characterize the immune response elicited by these particles as well as to determine their potential as an alternative to the use of live L. lactis for mucosal antigen delivery.

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“…They showed that passive immunization of 6 days old chicks with IgY obtained from egg yolks of hens immunized with C. jejuni lysates or fraction of C. jejuni hydrophobic proteins resulted not only in reduction their colonization by homologous C. jejuni strain but also reduce the pathogen transmission to not infected birds ( Hermans et al, 2014 ). More and more LAB, mainly members of the Lactococcus and Lactobacillus genera, have been tested as vehicles for the delivery of heterologous bacterial or viral antigens into animal mucosal immune systems ( Marelli et al, 2011 ; Villena et al, 2011 ; Kajikawa et al, 2012 ; Fontana et al, 2013 ; Li et al, 2014 ). In this work, we employed L. lactis because genetic engineering tools for this bacterium have been worked out in detail ( Fontana et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

Cell Wall Anchoring of the Campylobacter Antigens to Lactococcus lactis

et al. 2016

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Campylobacter jejuni is the most frequent cause of human food-borne gastroenteritis and chicken meat is the main source of infection. Recent studies showed that broiler chicken immunization against Campylobacter should be the most efficient way to lower the number of human infections by this pathogen. Induction of the mucosal immune system after oral antigen administration should provide protective immunity to chickens. In this work we tested the usefulness of Lactococcus lactis, the most extensively studied lactic acid bacterium, as a delivery vector for Campylobacter antigens. First we constructed hybrid protein – CjaA antigen presenting CjaD peptide epitopes on its surface. We showed that specific rabbit anti-rCjaAD serum reacted strongly with both CjaA and CjaD produced by a wild type C. jejuni strain. Next, rCjaAD and CjaA were fused to the C-terminus of the L. lactis YndF containing the LPTXG motif. The genes expressing these proteins were transcribed under control of the L. lactis Usp45 promoter and their products contain the Usp45 signal sequences. This strategy ensures a cell surface location of both analyzed proteins, which was confirmed by immunofluorescence assay. In order to evaluate the impact of antigen location on vaccine prototype efficacy, a L. lactis strain producing cytoplasm-located rCjaAD was also generated. Animal experiments showed a decrease of Campylobacter cecal load in vaccinated birds as compared with the control group and showed that the L. lactis harboring the surface-exposed rCjaAD antigen afforded greater protection than the L. lactis producing cytoplasm-located rCjaAD. To the best of our knowledge, this is the first attempt to employ Lactic Acid Bacteria (LAB) strains as a mucosal delivery vehicle for chicken immunization. Although the observed reduction of chicken colonization by Campylobacter resulting from vaccination was rather moderate, the experiments showed that LAB strains can be considered as an alternative vector to deliver heterologous antigens to the bird immune system. Additionally, the analysis of the structure and immunogenicity of the generated rCjaAD hybrid protein showed that the CjaA antigen can be considered as a starting point to construct multiepitope anti-Campylobacter vaccines.

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Oral immunization with recombinantLactococcus lactisdelivering a multi-epitope antigen CTB-UE attenuatesHelicobacter pyloriinfection in mice

Cited by 40 publications

References 34 publications

Lactic acid bacteria—20 years exploring their potential as live vectors for mucosal vaccination

Lactic acid bacteria—20 years exploring their potential as live vectors for mucosal vaccination

Rotavirus VP6 protein mucosally delivered by cell wall-derived particles from Lactococcus lactis induces protection against infection in a murine model

Cell Wall Anchoring of the Campylobacter Antigens to Lactococcus lactis

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