Vaccine strategies against cystic fibrosis pathogens

Moigne, Vincent Le; Gaillard, Jean‐Louis; Herrmann, Jean-Louis

doi:10.1080/21645515.2015.1102810

Cited by 4 publications

(3 citation statements)

References 74 publications

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“…Genetic diseases of the digestive system, such as cystic fibrosis, Crohn's disease, or Type 1 diabetes are also candidates for oral gene delivery (74,75). For example, vaccines against the cystic fibrosis pathogen, P. aeruginosa flagella, have been developed in various forms targeting its fusion proteins; furthermore, recently developed nasal and oral vaccinations resulted in airway immunogenicity against the pathogen with superior efficacy compared to systemic vaccination (75). Type 1 diabetes is a metabolic disease initiated by the autoimmune destruction of pancreatic insulin-producing beta cells and accompanied by the development of antigen-specific antibodies and cytotoxic T lymphocytes.…”

Section: Yeast-derived Oral Gene Delivery Disease Targetsmentioning

confidence: 99%

“…Since oral gene delivery must presently be confined to the GI system, potential disease targets for DNA vaccines include bacterial and viral gastritis, ulcers, and GI cancers. Genetic diseases of the digestive system, such as cystic fibrosis, Crohn’s disease, or Type 1 diabetes are also candidates for oral gene delivery [ 74 , 75 ]. For example, vaccines against the cystic fibrosis pathogen, P. aeruginosa flagella , have been developed in various forms targeting its fusion proteins; furthermore, recently developed nasal and oral vaccinations resulted in airway immunogenicity against the pathogen with superior efficacy compared to systemic vaccination [ 75 ].…”

Section: Disease Targets For Oral Yeast Systemsmentioning

confidence: 99%

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Yeasts in nanotechnology-enabled oral vaccine and gene delivery

Иванова

2021

Bioengineered

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Oral vaccine and gene delivery systems must be engineered to withstand several different physiological environments, such as those present in the oral cavity, stomach, and jejunum, each of which exhibits varying pH levels and enzyme distributions. Additionally, these systems must be designed to ensure appropriate gastrointestinal absorption and tissue/cellular targeting properties. Although a plethora of nanomaterials are employed in the construction of these delivery devices, yeasts display unique characteristics, such a rigid cell wall and a resistance to harsh environments, that make them a prime vehicle for oral delivery of active pharmaceutical agents, vaccines, and genetic material. The ability of yeast cells to adhere to other cells or substrates is a crucial property that allows for more efficient gastrointestinal passage and subsequent systemic circulation, which has enabled substantial advancements in therapeutic efficacy in the pharmaceutical arena. Among several discoveries, the feasibility of yeast for vaccine and gene delivery is supported by findings from recent studies that yeasts have the ability to independently activate or deactivate separate but co-functioning portions of the immune system to synergistically ameliorate treatment effects. The purpose of this review is to present current information on the uses of yeast in the development of oral vaccines and gene delivery systems with an emphasis on yeast-related mechanisms of immune system activation, along with potential clinical implications in terms of disease targets and approaches to formulations. ResultsThe oral route for delivery of vaccines and gene therapies offers a number of advantages, including ease of administration, manufacturing efficiency, and cost. However, before widespread adoption of this therapeutic modality can occur, factors such as adequate local and systemic availability of the therapeutic agent and accurate targeting of tissues and cells, are just some of the challenges that must be addressed. Yeasts-based delivery vehicles are excellent candidates for oral vaccine and oral gene therapies as many species possess cellular characteristics resulting in enhanced resistance to the harsh gastrointestinal (GI) environment and facilitated passage across the mucosal barrier. Yeast capsules can stimulate and modulate host immune responses, which is beneficial for vaccine efficacy. In addition, recombinant modification of yeasts to express cell penetrating proteins and injection mechanisms along with efficient cell adhering capabilities can potentially improve transfection rates of genetic material. In this literature review, we present evidence supporting the beneficial role yeast-based delivery systems can play in increasing the efficacy of oral administration of vaccines and gene therapies.

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Section: Yeast-derived Oral Gene Delivery Disease Targetsmentioning

confidence: 99%

Section: Disease Targets For Oral Yeast Systemsmentioning

confidence: 99%

Yeasts in nanotechnology-enabled oral vaccine and gene delivery

Иванова

2021

Bioengineered

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“…This is the case with the phospholipase C (PLC)-encoding gene, which not only was important for virulence in an M. abscessus mouse model of infection (12) but also exhibited potent vaccine properties in CF (⌬F508 FVB) mice immunized with plc-encoding DNA through the production of high anti-PLC antibody titers (13). As such, certain virulence factors may be viewed as relevant antigen targets for the development of protective vaccines against human pathogens (14)(15)(16).…”

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confidence: 99%

MgtC as a Host-Induced Factor and Vaccine Candidate against Mycobacterium abscessus Infection

et al. 2016

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g Mycobacterium abscessus is an emerging pathogenic mycobacterium involved in pulmonary and mucocutaneous infections, presenting a serious threat for patients with cystic fibrosis (CF). The lack of an efficient treatment regimen and the emergence of multidrug resistance in clinical isolates require the development of new therapeutic strategies against this pathogen. Reverse genetics has revealed genes that are present in M. abscessus but absent from saprophytic mycobacteria and that are potentially involved in pathogenicity. Among them, MAB_3593 encodes MgtC, a known virulence factor involved in intramacrophage survival and adaptation to Mg 2؉ deprivation in several major bacterial pathogens. Here, we demonstrated a strong induction of M. abscessus MgtC at both the transcriptional and translational levels when bacteria reside inside macrophages or upon Mg 2؉ deprivation. Moreover, we showed that M. abscessus MgtC was recognized by sera from M. abscessus-infected CF patients. The intramacrophage growth (J774 or THP1 cells) of a M. abscessus knockout mgtC mutant was, however, not significantly impeded. Importantly, our results indicated that inhibition of MgtC in vivo through immunization with M. abscessus mgtC DNA, formulated with a tetrafunctional amphiphilic block copolymer, exerted a protective effect against an aerosolized M. abscessus challenge in CF (⌬F508 FVB) mice. The formulated DNA immunization was likely associated with the production of specific MgtC antibodies, which may stimulate a protective effect by counteracting MgtC activity during M. abscessus infection. These results emphasize the importance of M. abscessus MgtC in vivo and provide a basis for the development of novel therapeutic tools against pulmonary M. abscessus infections in CF patients. Mycobacterium abscessus, a rapidly growing mycobacterium (RGM), is the etiological agent of a wide spectrum of infections in humans. M. abscessus is responsible for severe and persistent pulmonary infections, disseminated cutaneous diseases, and posttrauma and postsurgery wound infections, mostly in immunocompetent patients and in cystic fibrosis (CF) patients (1-5). Infections by this pathogen lead to a fatality rate that is higher than those seen with other RGM species. Infection of CF patients with M. abscessus is a major health-related issue in most CF centers worldwide (1, 2, 6, 7) and is considered a contraindication to lung transplantation, leaving these patients with minimal therapeutic options.M. abscessus provokes very challenging therapeutic issues because of its natural resistance to most available antibiotics (8-10) and is considered the most drug-resistant mycobacterial species. The lack of optimal therapeutic treatments and the emergence of multidrug resistance in M. abscessus stress the need for the discovery of new strategies to combat these infections.Reverse genetics, based on the comparison between pathogenic and nonpathogenic species, allows the identification of genes missing in nonpathogenic species and encoding potential virulence...

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