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“…[65] Oral immunization with the microcontainer vaccine did not elicit humoral or cellular immune responses. [65] However, serum IgG was observed when cubosomes were delivered orally without encapsulation in microcontainers, which suggests that the microcontainers may hinder vaccine bioavailability. Thus, the impact of cubosome vaccine protection in gastric conditions is confounded by the reduced function observed when delivered in microcontainers.…”
Section: Liposomal and Polymeric Particle Delivery Systemsmentioning
confidence: 96%
“…These cubic liquid‐crystalline nanoparticles can take on different geometries where physiochemically diverse drugs can be loaded in the separate phases, and the higher volume of lipids allows for larger drug encapsulation. Cubosomes formulated with dextran, OVA, and the adjuvant Quil‐A were loaded in templated cylindrical microcontainers made of the photoresist SU‐8 and coated with Eudragit L100‐55 for pH‐dependent cubosome release . Oral immunization with the microcontainer vaccine did not elicit humoral or cellular immune responses .…”
Section: Application Of Advanced Materials To Study Intestinal Immunologymentioning
confidence: 99%
“…Cubosomes formulated with dextran, OVA, and the adjuvant Quil‐A were loaded in templated cylindrical microcontainers made of the photoresist SU‐8 and coated with Eudragit L100‐55 for pH‐dependent cubosome release . Oral immunization with the microcontainer vaccine did not elicit humoral or cellular immune responses . However, serum IgG was observed when cubosomes were delivered orally without encapsulation in microcontainers, which suggests that the microcontainers may hinder vaccine bioavailability.…”
Section: Application Of Advanced Materials To Study Intestinal Immunologymentioning
Oral vaccines have the potential to reduce cost, improve compliance, and induce immunity at mucosal surfaces that are the first line of defense against infection. The gastrointestinal tract is highly evolved to efficiently digest and absorb nutrients without eliciting aberrant inflammation. However, these functions also limit the efficacy of immunization by the oral route. While mechanisms responsible for the development of tolerance to fed antigens are being illuminated, the application of materials with precise physiochemical properties and immunomodulatory potential may accelerate understanding of immunity within the gastrointestinal tract. Insight into these immunological mechanisms can inform the design of next‐generation oral vaccines to harness critical functions to elicit immunity. Here, material strategies for oral vaccines and their dual function in understanding and overcoming immunological barriers associated with oral immunization are discussed.
“…[65] Oral immunization with the microcontainer vaccine did not elicit humoral or cellular immune responses. [65] However, serum IgG was observed when cubosomes were delivered orally without encapsulation in microcontainers, which suggests that the microcontainers may hinder vaccine bioavailability. Thus, the impact of cubosome vaccine protection in gastric conditions is confounded by the reduced function observed when delivered in microcontainers.…”
Section: Liposomal and Polymeric Particle Delivery Systemsmentioning
confidence: 96%
“…These cubic liquid‐crystalline nanoparticles can take on different geometries where physiochemically diverse drugs can be loaded in the separate phases, and the higher volume of lipids allows for larger drug encapsulation. Cubosomes formulated with dextran, OVA, and the adjuvant Quil‐A were loaded in templated cylindrical microcontainers made of the photoresist SU‐8 and coated with Eudragit L100‐55 for pH‐dependent cubosome release . Oral immunization with the microcontainer vaccine did not elicit humoral or cellular immune responses .…”
Section: Application Of Advanced Materials To Study Intestinal Immunologymentioning
confidence: 99%
“…Cubosomes formulated with dextran, OVA, and the adjuvant Quil‐A were loaded in templated cylindrical microcontainers made of the photoresist SU‐8 and coated with Eudragit L100‐55 for pH‐dependent cubosome release . Oral immunization with the microcontainer vaccine did not elicit humoral or cellular immune responses . However, serum IgG was observed when cubosomes were delivered orally without encapsulation in microcontainers, which suggests that the microcontainers may hinder vaccine bioavailability.…”
Section: Application Of Advanced Materials To Study Intestinal Immunologymentioning
Oral vaccines have the potential to reduce cost, improve compliance, and induce immunity at mucosal surfaces that are the first line of defense against infection. The gastrointestinal tract is highly evolved to efficiently digest and absorb nutrients without eliciting aberrant inflammation. However, these functions also limit the efficacy of immunization by the oral route. While mechanisms responsible for the development of tolerance to fed antigens are being illuminated, the application of materials with precise physiochemical properties and immunomodulatory potential may accelerate understanding of immunity within the gastrointestinal tract. Insight into these immunological mechanisms can inform the design of next‐generation oral vaccines to harness critical functions to elicit immunity. Here, material strategies for oral vaccines and their dual function in understanding and overcoming immunological barriers associated with oral immunization are discussed.
“…However, from 24 h and onward, the BMP signal increased consistently reaching a maximum at day 10 of the study, after which it was decreased at day 14. The ionized PS (38:4) (m/z 810.529), which is the most abundant phosphatidylserine species in the lungs (38), was expressed in the lung sections at all studied time points (Supplementary Figure S6). Analysis of the signal intensity ratio of BMP (22:6/22:6) as compared to PS (38:4) (m/z 810.529) showed that the intensity ratio of BMP/PS was increased from 24 h post-administration, reached a threshold at day 10 of the study, after which it was decreased at day 14 ( Figure 9B).…”
Section: Increased Bmp Lipids In Alveloar Macrophages Following Intramentioning
Understanding the in vivo fate of vaccine antigens and adjuvants and their safety is crucial for the rational design of mucosal subunit vaccines. Prime and pull vaccination using the T helper 17-inducing adjuvant CAF01 administered parenterally and mucosally, respectively, has previously been suggested as a promising strategy to redirect immunity to mucosal tissues. Recently, we reported a promising tuberculosis (TB) vaccination strategy comprising of parenteral priming followed by intrapulmonary (i.pulmon.) mucosal pull immunization with the TB subunit vaccine candidate H56/CAF01, which resulted in the induction of lung-localized, H56-specific T cells and systemic as well as lung mucosal IgA responses. Here, we investigate the uptake of H56/CAF01 by mucosal and systemic innate myeloid cells, antigen-presenting cells (APCs), lung epithelial cells and endothelial cells in mice after parenteral prime combined with i.pulmon. pull immunization, and after parenteral or i.pulmon. prime immunization alone. We find that i.pulmon. pull immunization of mice with H56/CAF01, which are parenterally primed with H56/CAF01, substantially enhances vaccine uptake and presentation by pulmonary and splenic APCs, pulmonary endothelial cells and type I epithelial cells and induces stronger activation of dendritic cells in the lung-draining lymph nodes, compared with parenteral immunization alone, which suggests activation of both innate and memory responses. Using mass spectrometry imaging of lipid biomarkers, we further show that (i) airway mucosal immunization with H56/CAF01 neither induces apparent local tissue damage nor inflammation in the lungs, and (ii) the presence of CAF01 is accompanied by evidence of an altered phagocytic activity in alveolar macrophages, evident from
“…Such polymer is commonly applied to protect APIs from the harsh gastric environment (enzymes and low pH). The fabrication of microcontainers and techniques for loading and coating, are well described in literature [17] , [20] , [24] . Fig.…”
Section: Validation and Characterizationmentioning
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