Intestinal immune system and immune responses after administration of particulate vaccine. After particulate antigens are taken up at the inductive sites, they are presented to DCs. These antigen-loaded DCs prime naı¨ve CD4+ T-cells in the PPs. The primed CD4+ T-cells in turn trigger B-cells and undergo isotype switching to generate antigen-specific IgA+ B-cells. These IgA+ B-cells leave the PPs through afferent lymph to mesenteric lymph node and finally reach the blood circulation. Similarly, antigen-presenting DCs actively migrate to the mesenteric lymph nodes for further CD4+ T-cell activation and subsequent IgA+ B-cell production. The IgA+ B-cells further leave mesenteric lymph nodes to the blood circulation. The circulating antigen-specific IgA+ B-cells move to distant effector sites in the LP and undergo differentiation and maturation to generate high-affinity IgA+ producing plasma cells (enhanced by cytokines IL-5 and IL-6, subsets of Th2 cells), which in turn produce dimeric or polymeric forms of IgA. The dimeric or polymeric IgA binds to Ig receptors expressed on the basolateral surface of epithelial cells to form SIgA. (D) This complex is further transcytosed toward the luminal surface of the intestine (effector sites). Alternatively, particulate antigens directly reach the systemic circulation from the gut and interact with T-cells in the peripheral lymph nodes. DCs: Dendritic cells; LP: Lamina propria; PPs: Peyer’s patches; SIgA: Secretory IgA.
Nanoparticle based oral delivery of vaccines
Oral Delivery of
Presented by: Ashok Patidar
M.S.(Pharm) Natural Products
Registration no. NK19NPM332
NATIONAL INSTITITE OF PHARMACEUTICAL EDUCATION AND RESEARCH
Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Govt. of India
• Nanoparticles are sub-nanosized colloidal structures composed of
synthetic or semi-synthetic polymers that exist on a nanometre scale.
• Size range : 10–1000 nm
• They can possess physical properties such as uniformity, conductance
or special optical properties that make them desirable in materials
science and biology.
• Vaccines are composed of antigens, which may be live-attenuated,
inactivated, killed organisms or minimal fractions of pathogenic
organisms including proteins or peptides responsible for producing
the desired immune response against infections
• Oral delivery of vaccines represents the most attractive mode of
administration over other routes of delivery due to the fact that the
oral vaccination is
• Noninvasive and safe
• Simple to execute
• Showing good patient compliance
• Clinical practicality
• Several formulations based on nanoparticle strategies are currently
being explored to prepare stable oral vaccine formulations.
Properties of an ideal oral vaccine
• Low cost
• Easy administration without medical professionals and special devices
• Capacity for large-scale production
• Stability under lyophilization and avoidance of cold-chain storage
• Sufficient protection of antigens against gastrointestinal fluids
• High antigen loading/encapsulating capacity of particles
• Strong mucosal adjuvanticity
• Prolonged exposure of antigens to antigen-presenting cells
• Optimum size for effective transportation of particles across intestinal lumen
• Sufficient targeting ability to intestinal cells (microfold-cells)
• Produce long-term mucosal and systemic immunity
• Adequate safety profile
Oral mucosal vaccines (licensed and under clinical
Nanoparticle based oral vaccine delivery
• NPs can be engineered to encapsulate vaccine components inside or
attached to their surfaces for efficient presentation to APCs.
• NPs based carriers can be decorated with functional molecules to
target the immune cells, enhance stability and modify the release
property of antigens.
• NP-based vaccine delivery has been gaining popularity due to its
ability to co-deliver antigens and adjuvants in a single particulate
Various barriers in the gastrointestinal system encountered by oral vaccines and nanoparticulate vaccine
strategies to overcome these problems
Nano particulate vaccines transport across
luminal region of the intestine
(A) Phagocytosis by indwelling macrophages in the M-cell. (B) DC-mediated luminal sampling from the M-cells. (C)
Transepithelial DC extension into the luminal region of the intestine. (D) Goblet cell-mediated transport of low molecular
weight soluble antigens to CD103+ DCs. (E) Enterocytic receptor-mediated transport (FcRn receptor). (F) Transcellular
transport across the enterocytes. (G) Paracellular transport between the walls of enterocytes. DCs: Dendritic cells; M-cell:
Intestinal immune system and immune
responses after administration of particulate
(A) After particulate antigens are taken up
at the inductive sites, they are
presented to DCs.
(B) Antigen-presenting DCs actively migrate
to the mesenteric lymph nodes for
further CD4+ T-cell activation and
subsequent IgA+ B-cell production.
(C) The dimeric or polymeric IgA binds to Ig
receptors expressed on the basolateral
surface of epithelial cells to form SIgA.
(D) The complex is further transcytosed
toward the luminal surface of the
intestine (effector sites).
DCs: Dendritic cells; LP: Lamina propria; PPs:
Peyer’s patches; SIgA: Secretory IgA
Nanoparticle interaction with antigen
• Vaccine formulations comprising nanoparticles and antigens can be
classified by nanoparticle action into those based on delivery system
and immune potentiator approaches.
• A delivery system, nanoparticles can deliver antigen to the cells of
the immune system, i.e. the antigen and nanoparticle are co-ingested
by the immune cell, or act as a transient delivery system, i.e. protect
the antigen and then release it at the target location.
• Immune potentiator approaches: nanoparticles activate certain
immune pathways which might then enhance antigen processing and
Interaction of nanoparticle with antigen of
Types of interaction:
2. Immune stimulator:
• Clearance of nanoparticles could be achieved through degradation by
the immune system or by renal or biliary clearance.
• biliary clearance through liver allows excretion of nanoparticles larger
than 200 nm.
• Renal clearance through kidneys can excrete nanoparticles smaller
than 8 nm.
• Surface charge that follows the order of positively-charged < neutral
< negatively charge.
Techniques to determine interaction
with Immune cells
Many different in vivo molecular imaging techniques used are
magnetic resonance imaging (MRI)
positron emission tomography (PET),
fluorescence imaging, single photon emission computed tomography
X-ray computed tomography (CT)
Superparamagnetic iron oxide nanoparticles (SPION)
Pros and cons of oral nanoparticle
• The main challenges associated with oral vaccine delivery are sufficient protection of the
integrity of the antigens and effective transportation across the intestinal epithelium.
• Efficacy of oral vaccines is mostly hampered by the low population of microfold-cells (M-
cells) in the intestines.
• An alternative novel targeted delivery system is sought for effective delivery of oral
vaccines to M-cells, intestinal dendritic cells and enterocytes.
• Several polymer and lipid-based nanocarriers have shown potential to enhance the
immunogenicity of oral vaccines; however, there is no clear specific mechanism
identified to show how these carriers promote enhanced mucosal and immune
• Certain modifications of existing nanoparticulate delivery systems may drastically change
stability/efficacy of vaccines. For example, bilosomes in contrast to liposomes have
shown greatly improved stability in the gastrointestinal tract and during
• Further developments in nanoparticle vaccines should concentrate on simple and robust
design of the formulations for easy scale-up and commercialization.
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