**4. Oral vaccine delivery system**

Vaccination is one of the most cost-effective approaches to prevent infectious diseases such as hepatitis B, tetanus, polio, and rabies. Vaccines contain pathogens, either live-attenuated, inactive or killed antigen [75]. These pathogens will be administered in the body and recognised by the immune system.

The oral delivery of vaccines is quite challenging as the pathogen is introduced into the body. It is mandatory to ensure mucosal immune response works effectively to protect the body against the pathogen and their toxin [54].

As the vaccine enters the intestine, its presence will trigger the inductive site, the Peyer's patches. The Peyer's patches consist of M-cell which will allow the entry of the antigen through endocytosis. The antigen then will be transported into intraepithelial dendritic cells or macrophages and be taken up by the cell through phagocytosis [76].

The antigen-loaded dendritic cell will present the antigen fragment on its surface and triggers the activation of naive CD4+ T-cells. The activated CD4+ T-cells will bind to the antigen fragment, MHC class II. This binding releases chemical mediators, interleukin-2 (IL-2), that function to regulate the activity of lymphocytes for immunity. IL-2 stimulates the cell division of CD4+ T-cells, activates B-cells and cytotoxic T-cells. B-cell is responsible for mediating humoral immunity by differentiating into plasma cells. Plasma cells will generate antibodies to fight against pathogens [77].
