Enhancing Oral Vaccine Potency by Targeting Intestinal M Cells

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

Analysis of Interactions of Salmonella Type Three Secretion Mutants with 3-D Intestinal Epithelial Cells

The prevailing paradigm of Salmonella enteropathogenesis based on monolayers asserts that Salmonella pathogenicity island-1 Type Three Secretion System (SPI-1 T3SS) is required for bacterial invasion into intestinal epithelium. However, little is known about the role of SPI-1 in mediating gastrointestinal disease in humans. Recently, SPI-1 deficient nontyphoidal Salmonella strains were isolated from infected humans and animals, indicating that SPI-1 is not required to cause enteropathogenesis and demonstrating the need for more in vivo-like models. Here, we utilized a previously characterized 3-D organotypic model of human intestinal epithelium to elucidate the role of all characterized Salmonella enterica T3SSs. Similar to in vivo reports, the Salmonella SPI-1 T3SS was not required to invade 3-D intestinal cells. Additionally, Salmonella strains carrying single (SPI-1 or SPI-2), double (SPI-1/2) and complete T3SS knockout (SPI-1/SPI-2: flhDC) also invaded 3-D intestinal cells to wildtype levels. Invasion of wildtype and TTSS mutants was a Salmonella active process, whereas non-invasive bacterial strains, bacterial size beads, and heat-killed Salmonella did not invade 3-D cells. Wildtype and T3SS mutants did not preferentially target different cell types identified within the 3-D intestinal aggregates, including M-cells/M-like cells, enterocytes, or Paneth cells. Moreover, each T3SS was necessary for substantial intracellular bacterial replication within 3-D cells. Collectively, these results indicate that T3SSs are dispensable for Salmonella invasion into highly differentiated 3-D models of human intestinal epithelial cells, but are required for intracellular bacterial growth, paralleling in vivo infection observations and demonstrating the utility of these models in predicting in vivo-like pathogenic mechanisms

Rotavirus vaccine efficacy: current status and areas for improvement

The difference noted in Rotavirus vaccine efficiency between high and low income countries correlates with the lack of universal access to clean water and higher standards of hygiene. Overcoming these obstacles will require great investment and also time, therefore more effective vaccines should be developed to meet the needs of those who would benefit the most from them. Increasing our current knowledge of mucosal immunity, response to Rotavirus infection and its modulation by circadian rhythms could point at actionable pathways to improve vaccination efficacy, especially in the case of individuals affected by environmental enteropathy. Also, a better understanding and validation of Rotavirus entry factors as well as the systematic monitoring of dominant strains could assist in tailoring vaccines to individual’s needs. Another aspect that could improve vaccine efficiency is targeting to M cells, for which new ligands could potentially be sought. Finally, alternative mucosal adjuvants and vaccine expression, storage and delivery systems could have a positive impact in the outcome of Rotavirus vaccination

Epithelial M Cells: differentiation and function.

M cells are distinctive epithelial cells that occur only in the follicle-associated epithelia that overlie organized mucosa-associated lymphoid tissues. They are structurally and functionally specialized for transepithelial transport, delivering foreign antigens and microorganisms to organized lymphoid tissues within the mucosae of the small and large intestines, tonsils and adenoids, and airways. M cell transport is a double-edged sword: Certain pathogens exploit the features of M cells that are intended to promote uptake for the purpose of immunological sampling. Eludication of the molecular architecture of M cell apical surfaces is important for understanding the strategies that pathogens use to exploit this pathway and for utilizing M cell transport for delivery of vaccines to the mucosal immune system. This article reviews the functional and biochemical features that distinguish M cells from other intestinal cell types. In addition it synthesizes the available information on development and differentiation of organized lymphoid tissues and the specialized epithelium associated with these immune inductive sites

Recent advances in oral vaccine development: yeast-derived β-glucan particles

Oral vaccination is the most challenging vaccination method due to the administration route. However, oral vaccination has socio-economic benefits and provides the possibility of stimulating both humoral and cellular immune responses at systemic and mucosal sites. Despite the advantages of oral vaccination, only a limited number of oral vaccines are currently approved for human use. During the last decade, extensive research regarding antigen-based oral vaccination methods have improved immunogenicity and induced desired immunological outcomes. Nevertheless, several factors such as the harsh gastro-intestinal environment and oral tolerance impede the clinical application of oral delivery systems. To date, human clinical trials investigating the efficacy of these systems are still lacking. This review addresses the rationale and key biological and physicochemical aspects of oral vaccine design and highlights the use of yeast-derived β-glucan microparticles as an oral vaccine delivery platform