Nano and Microparticles as Potential Oral Vaccine Carriers and Adjuvants Against Infectious Diseases

Abstract

Mucosal surfaces are the first site of infection for most infectious diseases and oral vaccination can provide protection as the first line of defense. Unlike systemic administration, oral immunization can stimulate cellular and humoral immune responses at both systemic and mucosal levels to induce broad-spectrum and long-lasting immunity. Therefore, to design a successful vaccine, it is essential to stimulate the mucosal as well as systemic immune responses. Successful oral vaccines need to overcome the harsh gastrointestinal environment such as the extremely low pH, proteolytic enzymes, bile salts as well as low permeability and the low immunogenicity of vaccines. In recent years, several delivery systems and adjuvants have been developed for improving oral vaccine delivery and immunogenicity. Formulation of vaccines with nanoparticles and microparticles have been shown to improve antigen stability, availability and adjuvanticity as well as immunostimulatory capacity, target delivery and specific release. This review discusses how nanoparticles (NPs) and microparticles (MPs) as oral carriers with adjuvant characteristics can be beneficial in oral vaccine development.

Keywords: infectious diseases; microparticles; nanoparticles; oral vaccines; vaccine carriers.

FIGURE 1

Schematic diagram of mucosal immune induction to generate T-cell-dependent IgA production. The particulate antigens in intestinal lumen are moved across the intestinal epithelium barrier by sampling M cells, transcytosed and presented to DCs. The antigen-loaded DCs (activated DCs) could travel and prime naïve CD4 T cells in Peyer’s patches. Primed CD4 T cells then activate B cells, which undergo isotype switching, thus generating antigen-specific IgA⁺ B cells. These IgA⁺ B cells leave the Peyer’s patches through the afferent lymph system to mesenteric lymph node, enter the blood circulation and reach effector sites in the lamina propria, mature, and become IgA producing-plasma B cells. The dimeric or polymeric IgA binds to Ig receptors expressed on the basolateral surface of epithelial cells to form SIgA. The figure is made with biorender (https://biorender.com/).

FIGURE 2

Timeline of licensed vaccine adjuvants. Aluminium salt was the first and most used adjuvant with other limited adjuvants such as MF59, virosome, AS01, AS03, AS04 and CpG ODN which are used in FDA-approved vaccines for humans.