An updated review on oral protein-based antigen vaccines efficiency and delivery approaches: a special attention to infectious diseases

Various infectious agents affect human health via the oral entrance. The majority of pathogens lack approved vaccines. Oral vaccination is a convenient, safe and cost-effective approach with the potential of provoking mucosal and systemic immunity and maintaining individual satisfaction. However, vaccines should overcome the intricate environment of the gastrointestinal tract (GIT). Oral protein-based antigen vaccines (OPAVs) are easier to administer than injectable vaccines and do not require trained healthcare professionals. Additionally, the risk of needle-related injuries, pain, and discomfort is eliminated. However, OPAVs stability at environmental and GIT conditions should be considered to enhance their stability and facilitate their transport and storage. These vaccines elicit the local immunity, protecting GIT, genital tract and respiratory epithelial surfaces, where numerous pathogens penetrate the body. OPAVs can also be manipulated (such as using specific incorporated ligand and receptors) to elicit targeted immune response. However, low bioavailability of OPAVs necessitates development of proper protein carriers and formulations to enhance their stability and efficacy. There are several strategies to improve their efficacy or protective effects, such as incorporation of adjuvants, enzyme inhibitors, mucoadhesive or penetrating devices and permeation enhancers. Hence, efficient delivery of OPAVs into GIT require proper delivery systems mainly including smart target systems, probiotics, muco-adhesive carriers, lipid- and plant-based delivery systems and nano- and microparticles.