Enhancing Oral Vaccine Potency by Targeting Intestinal M Cells

Abstract

The immune system in the gastrointestinal tract plays a crucial role in the control of infection, as it constitutes the first line of defense against mucosal pathogens. The attractive features of oral immunization have led to the exploration of a variety of oral delivery systems. However, none of these oral delivery systems have been applied to existing commercial vaccines. To overcome this, a new generation of oral vaccine delivery systems that target antigens to gut-associated lymphoid tissue is required. One promising approach is to exploit the potential of microfold (M) cells by mimicking the entry of pathogens into these cells. Targeting specific receptors on the apical surface of M cells might enhance the entry of antigens, initiating the immune response and consequently leading to protection against mucosal pathogens. In this article, we briefly review the challenges associated with current oral vaccine delivery systems and discuss strategies that might potentially target mouse and human intestinal M cells.

Roles of M cells in infection and mucosal vaccines

“…74 The appearance of a new potent mucosal vaccine also brings other challenges, such as antigen degradation by proteolytic activities, low dose of antigen absorbed, and lack of potent mucosal adjuvants. 60 We need to probe oral vehicle delivery systems more deeply to overcome these issues. The capacity of M cells to sample antigens, transfer luminal bacteria, and stimulate mucosal immune responses, makes them fascinating targets for mucosal vaccine delivery.…”

“…72 The number of M cell receptors and their ligands that have been identified so far is limited, and most of them are not just expressed in M cells, but in neighboring enterocytes as well. 60 Toll-like receptor (TLR)-4 and a5b1 integrin, belonging to pathogen recognition receptors (PRRs), are expressed on the surface of human and mouse M cells. Interaction between these innate immune system molecules with pathogen-associated molecular patterns is essential for bacteria translocation across the lumen.…”

“…For example, a5b1 integrin is both dispersed on the lateral and basolateral surfaces of enterocytes and on the apical surface of M cells, which is a challenge in targeting M cells alone. 60 M-cell-targeting ligands can enhance the uptake of oral vaccines by M cells and improve antigen-specific immune responses in both mucosal and systemic immunity. It seems that targeting ligand to antigen is a very promising approach in the development of efficient mucosal vaccine.…”

Characterization and optimization of bilosomes for oral vaccine delivery

“…Previous research has shown that delivering subunit antigens alone via the oral route does not sufficiently promote effective immune responses (Azizi et al, 2010). Indeed when considering recombinant influenza antigen, Amorij, et al (2007) have shown that the intragastric delivery of recombinant H3N2 antigen alone induced low HI titres, which were significantly lower than the antigen delivered IM (Amorij et al, 2007).…”

Prevention of Allergy: From Immunology of Pregnancy To Infant Feeding in the First Months of Life

“…Их роль состоит в пре-зентации антигенов иммунокомпетентным клеткам в пейеровых бляшках, с которыми М клетки связаны анатомически. Этот процесс является важнейшим этапом становления толерантности [15].…”