Pollen grains for oral vaccination

Abstract

Oral vaccination can offer a painless and convenient method of vaccination. Furthermore, in addition to systemic immunity it has potential to stimulate mucosal immunity through antigen-processing by the gut-associated lymphoid tissues. In this study we propose the concept that pollen grains can be engineered for use as a simple modular system for oral vaccination. We demonstrate feasibility of this concept by using spores of Lycopodium clavatum (clubmoss) (LSs). We show that LSs can be chemically cleaned to remove native proteins to create intact clean hollow LS shells. Empty pollen shells were successfully filled with molecules of different sizes demonstrating their potential to be broadly applicable as a vaccination system. Using ovalbumin (OVA) as a model antigen, LSs formulated with OVA were orally fed to mice. LSs stimulated significantly higher anti-OVA serum IgG and fecal IgA antibodies compared to those induced by use of cholera toxin as a positive-control adjuvant. The antibody response was not affected by pre-neutralization of the stomach acid, and persisted for up to seven months. Confocal microscopy revealed that LSs can translocate in to mouse intestinal wall. Overall, this study lays the foundation of using LSs as a novel approach for oral vaccination.

Lycopodium Spores: A Naturally Manufactured, Superrobust Biomaterial for Drug Delivery

“…[30][31][32] Most conventional techniques used for encapsulation such as emulsion solvent evaporation, spray drying, and chemical conjugation fail to reliably provide either size monodispersity or well-defi ned microstructures. [ 26,27,[30][31][32] Although several studies have reported the use of empty exine microcapsules for the encapsulation of drugs, vaccines, and magnetic resonance imaging (MRI) contrast agents, as well as for use in cosmetics and food supplements, [ 7,[16][17][18]22 ] the use of the natural "spores" as a microencapsulation material and delivery vehicle still remains unexplored. In this regard, we have directed our efforts toward exploring systems to produce macromoleculeloaded spores using three different microencapsulation techniques.…”

“…[ 1 ] L. clavatum spores are used in traditional herbal medicine and have been shown to exhibit a wide range of therapeutic benefi ts including improved osteogenesis, [ 11 ] improved cognitive function, [ 12 ] treatment of gastrointestinal disorders, [ 8 ] hepatoprotective activity, [ 13 ] and antioxidative properties. [ 14 ] Recent studies have demonstrated the use of processed L. clavatum shells for encapsulation, [15][16][17][18][19] however, the production of L. clavatum sporopollenin capsules requires the prolonged processing of natural spores with harsh chemical treatments at elevated temperatures, so as to isolate the sporopollenin exine shell. [20][21][22][23][24] In many applications, this extensive processing may be unnecessary and potential therapeutic benefi ts may be lost.…”

Pollen fillers for reinforcing and strengthening of epoxy composites

“…Due to their complex biologically derived morphology, these mimics may provide unique function as fillers. In addition, pollen exine has been proposed as vehicles for the delivery of pharmaceuticals and vaccines [14,15].…”

Sporopollenin, The Least Known Yet Toughest Natural Biopolymer

“…Applications as microcapsules: the capability of exines from L. clavatum to act as microcapsules (Figure 1) was demonstrated ) for a range of polar and non-polar materials, over a wide range of molecular weights, from water to proteins up to 2000 kDa (Atwe et al, 2014). Notably, neither the sporopollenin nor the encapsulation procedure was significantly deleterious to the enzymes' activity, thus offering the possibility of the exines to act as micro-reaction vessels or transporters of enzymes.…”

“…The mechanism involved may be associated with bioadhesion of the exine capsules in the gastrointestinal tract. A later in vivo study in mouse showed that the sporopollenin exines filled with ovalbumin as a model antigen could be used for oral immunization and which demonstrates the potential of the exines to be used for oral vaccination (Atwe et al, 2014). The authors offered evidence by confocal microscopy that the exines translocate across the mouse intestinal epithelium, which, the authors proposed, might be involved in the stimulation of the immune system.…”