Abstract
Most of the infectious diseases due to pathogens are caused by the mucosal tract penetration. Hence, vaccines delivered directly to the mucosal tissues can defend pathogenic infections and provide protection at the first site of infection. Thus, mucosal, specifically, oral delivery is becoming the most ideal mode of vaccination. However, oral vaccines have to overcome numerous barriers such as the extremely low pH of the stomach, the presence of proteolytic enzymes and bile salts as well as low permeability in the intestine. Several formulations based on nanoparticles like liposomes, solid solutions, emulsions, VLPs are currently being used to prepare stable oral vaccine formulations. In current days different companies are trying to develop oral vaccine for COVID 19 also. This review briefly discusses several vaccine development criteria their mechanisms and various aspects of oral nanoparticles-based vaccine design that should be considered for improved mucosal and systemic immune responses. 
 Keywords: Vaccine development, nanoparticles, liposome, VLP, COVID 19, mucosal immunity.
Highlights
After the penetration of pathogenic microorganisms in our body, they instantly start to invade and multiply to extend their soldiers against body’s immunity system resulting infection
Most of the infectious diseases due to pathogens are caused by the mucosal tract penetration
Several formulations based on nanoparticles like liposomes, solid solutions, emulsions, virus-like particles (VLPs) are currently being used to prepare stable oral vaccine formulations
Summary
After the penetration of pathogenic microorganisms in our body, they (germs) instantly start to invade and multiply to extend their soldiers against body’s immunity system resulting infection. An effective vaccine should have some capabilities & designs to elicit mucosal immunization like (i) overcoming mucosal barriers, (ii) targeting mucosal APCs or M cells for adequate antigen processing and T- or B-cell activation, and (iii) capability of modulating the kinetics of antigen and adjuvant presentation for induction of proper immunological memory responses. Nanotechnology-based drug delivery systems are capable of overcoming physiological barriers of the mucosa, can efficiently target immune cells, and control antigen kinetics. Different types of nanoparticle-based delivery systems have been invented for vaccine delivery to mucosal surfaces These inventions include liposomes, polymeric nanoparticles, lipid-polymer hybrid nanoparticles, emulsions, virus-like particles (VLPs), dendrimers, and immune stimulatory complexes (ISCOMs) (Table 2). Needled-vaccine generally produce robust & effective immune response at cellular & systemic level to prevent the disease, local effect, whereas oral vaccine delivery produces cellular, systemic & mucosal effect against pathogens. The evidence found from clinical trial phase I for Vaxart’s vaccine that its is capable of elicit CD8+ T-cell response, as measured by IFN-g and TNF-a induction which is more efficacious than Moderna or Pfizer mRNA vaccine. [65]
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