Oral Immunization of FMDV Vaccine Using pH-Sensitive and Mucoadhesive Thiolated Cellulose Acetate Phthalate Microparticles

Abstract

Several barriers such as gastric pH, enzymatic degradation and rapid transit should be overcome to orally deliver antigens for taking up by epithelial microfold cells in Peyer's patches of small intestine. To solve the above mentioned problems, we designed pH-sensitive and mucoadhesive polymeric microparticles (MPs) prepared by double emulsion technique using cellulose acetate phthalate (CAP) to enhance immune response of foot-and-mouth disease (FMD) virus (FMDV) subunit vaccine. Thiolation of CAP improved mucoadhesive property of CAP to prolong the MPs transit time through the gastrointestinal tract. Thiolated CAP (T-CAP) also slowed down antigen release in acidic pH of stomach but released more antigens in neutral pH of small intestine due to the pH-sensitivity of the T-CAP. Oral immunization of a chimerical multi-epitope recombinant protein as the FMD subunit vaccine via T-CAP MPs effectively delivered the vaccine to Peyer's patches eliciting mucosal IgA response. It will make a step forward into a promising oral subunit vaccine development in livestock industry. Keywords pH-senstive Á Mucoadhesive Á Foot-and-mouth disease Á Subunit vaccine Á Oral immunization Ho-Bin Lee and So-Yeon Yoon have contributed equally to this work.

Biodegradable polymers for modern vaccine development

“…Cellulose acetate phthalate (CAP) is and anionic polymer composed of phthalic acid and acetate [141]. Thiolated polymers have been intensively used as mucoadhesive polymers because these polymers can form covalent bond between thiol groups of thiolated polymer and cysteine rich subdomain of mucus glycoproteins through disulfide bonds [141].…”

“…Thiolated polymers have been intensively used as mucoadhesive polymers because these polymers can form covalent bond between thiol groups of thiolated polymer and cysteine rich subdomain of mucus glycoproteins through disulfide bonds [141]. M5BT protein as a subunit vaccine for the FMD was encapsulated into T-CAP microparticles (MPs) [141]. It is important to develop vaccine delivery carrier to prevent disease infected through mucosa [141].…”

“…M5BT protein as a subunit vaccine for the FMD was encapsulated into T-CAP microparticles (MPs) [141]. It is important to develop vaccine delivery carrier to prevent disease infected through mucosa [141]. CAP also has anti-HIV-1 activity.…”

Oral Delivery of Probiotics Using pH-Sensitive Phthalyl Inulin Tablets

“…Recently, polymeric delivery systems have been attracting attention as a means to deliver biological materials, proteins, genes, and chemotherapeutics because they can deliver drugs to target sites [10]. Among many strategies for orally delivering probiotics, pH-sensitive polymers, such as hydroxypropyl methylcellulose phthalate (HPMCP) [11], hydroxypropylmethyl cellulose acetated succinate [12], and cellulose acetate phthalate (CAP) [13] have been used to protect probiotics from harsh gastric conditions since probiotics loaded into pH-sensitive polymers cannot be released in an acidic pH environment due to the deprotonated carboxylic acids in the polymers [14]. However, because these pHsensitive polymers only have the ability to protect probiotics from harsh gastric conditions, we designed a new type of pH-sensitive polymer using inulin as a prebiotic.…”

Chemical Modification of Chitosan for Efficient Vaccine Delivery

“…A vaccine is a biological agent that provides active acquired immunity to a particular disease. A successful vaccine is one of the most cost-effective alternatives for controlling the incidence and mortality of diseases such as influenza [ 1 ], cholera [ 2 ], bubonic plague [ 3 ], hepatitis A [ 4 ], yellow fever [ 5 ], measles [ 6 ], mumps [ 7 ], rubella [ 8 ], tetanus [ 9 ], diphtheria [ 10 ], animal disease [ 11 ], etc.…”