Yeasts in nanotechnology-enabled oral vaccine and gene delivery

Abstract

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.

Enhancing the Effect of Nucleic Acid Vaccines in the Treatment of HPV-Related Cancers: An Overview of Delivery Systems

“…Yeasts are versatile single-celled microorganisms commonly used in the food industry that have potential application value as biofactories of therapeutic proteins and carriers of biological molecules [179]. Some strains have been certified as generally recognized as safe (GRAS) by the FDA and have been used for bioproduction [192]. Yarrowia lipolytica, Schizosaccharomyces pombe, Kluyveromyces lactis, Pichia pastoris, and Saccharomyces cerevisiae are predominantly used as carriers for drug delivery, subunit vaccine production, and recombinant proteins [178,192].…”

“…Some strains have been certified as generally recognized as safe (GRAS) by the FDA and have been used for bioproduction [192]. Yarrowia lipolytica, Schizosaccharomyces pombe, Kluyveromyces lactis, Pichia pastoris, and Saccharomyces cerevisiae are predominantly used as carriers for drug delivery, subunit vaccine production, and recombinant proteins [178,192]. In addition, they have been evaluated as a vehicle for nucleic acids, presenting several advantages, such as oral delivery capability, adjuvant activity, absence of toxicity, and specific delivery [178].…”

“…These promote immunostimulation by binding with dectin receptors, mannose-fucose, and Toll-like receptors (TLRs) such as TLR-2, 4, and 6 in DCs [138]. This interaction leads to the secretion of Th1 and Th17-type cytokines through pathogen-associated molecular patterns (PAMPs) and the activation of innate immunity components, inducing a specific APC uptake [192]. After being phagocytosed, they are degraded by phagolysosomes, and the nucleic acid is released and transported to their synthesis regions [178].…”

“…Oral vaccines are valued in developing countries as potential strategies for improving the effectiveness of vaccine delivery, reducing administration costs, and increasing vaccine adherence [208]. However, the oral route may not be the most suitable route for targeting lymph nodes given the existence of gastrointestinal tract barriers, low pH, and the presence of enzymes [192]. Systems based on bacteria can administer nucleic acid vaccines orally; however, they are more susceptible to chemical and physical barriers than yeast-containing β-glucan [176].…”

Study of the persistence and dynamics of recombinant mCherry‐producing Yarrowia lipolytica strains in the mouse intestine using fluorescence imaging

“…Yeasts combine the ease of use of microorganisms with a eukaryotic organization enabling post-translational protein modification and suitable glycosylation, which makes them preferred over other microbial systems for the production of recombinant therapeutic proteins (Ivanova, 2021;Kim et al, 2015;Lee et al, 2015;Madhavan et al, 2021;Patra et al, 2021;Pöhlmann et al, 2013). Y. lipolytica is a dimorphic oleaginous yeast that has drawn the attention of industrialists in the 1950s and has since been recognized as a powerful host for the expression, secretion and surface display of heterologous proteins, as well as a promising source of engineered cell factories for a wide range of applications (Madzak, 2018(Madzak, , 2021a.…”